Volume 31,2023 Issue 7

• Establishment of model of acute exacerbation of idiopathic pulmonary fibrosis in rats induced by bleomycin and lipopolysaccharide

  YU Ruizhi, WANG Tianjiao, ZANG Ningzi, LYU Xiaodong, PANG Lijian

  2023,31(7):833-845, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 001

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  Objective　To explore the method of establishing the animal model of acute exacerbation of idiopathic pulmonary fibrosis in rat, and explore the usage and dosage of the inducer lipopolysaccharide. Methods　150 healthy male Wister rats were randomly divided into negative control group (Control group), remission control group (IPF group), acute exacerbation control group (BLM group), lipopolysaccharide low dose group (LPS-low group), lipopolysaccharide medium dose group (LPS-mid group), and lipopolysaccharide high dose group (LPS-high group). The Control group was induced by first intratracheal injection of 0. 9% sodium chloride injection combined with second intraperitoneal injection of 0. 9% sodium chloride injection(day 0, 0. 1 mL/100 g; day 28, 0. 5 mL/100 g). The IPF group was induced by the first intratracheal injection of bleomycin combined with the second intraperitoneal injection of 0. 9% sodium chloride injection (day 0, 5 mg/ mL, 0. 1 mL/100 g; day 28, 0. 5 mL/100 g). The BLM group was induced by two consecutive intratracheal injections of bleomycin (day 0, 5 mg/ mL, 0. 1 mL/100 g; day 28, 7 mg/ mL, 0. 1 mL/100 g). LPS-low group, LPS-mid group and LPS-high group were induced by the first intratracheal injection of bleomycin combined with the second intraperitoneal injection of lipopolysaccharide (day 0, bleomycin, 5 mg/ mL, 0. 1 mL/100 g; day 28, lipopolysaccharide, 2.5 mg/ mL, 5 mg/ mL, 7.5 mg/ mL, 0. 5 mL/100 g). Take samples on the 31st, 35th, and 42nd days after the first molding. Observe the survival status of rats, lung tissue wet to dry weight ratio (W/ D), lung coefficient, lung tissue HE staining, lung tissue Masson staining, lung CT, lung function, arterial blood gas analysis, bronchoalveolar lavage fluid (BALF) composition analysis (total cell count, neutrophil count, IL-6 mass concentration, TNF-α mass concentration), lung tissue hydroxyproline (HYP) content, and lung tissue α-SMA immunohistochemistry analysis. Results　(1) The LPS-low group, LPS-mid group, and LPS-high group rats showed significant wheezing, dyspnea, cyanosis of the paw lips, decreased body mass, and increased mortality rate. (2) The W/ D value and lung coefficient of rats in LPS-low group, LPS-mid group and LPS-high group increased significantly, and acute pulmonary edema appeared. The performance of LPSmid group and BLM group was more consistent (P> 0. 05). (3) The histopathological changes in the LPS-low, LPS-mid, and LPS-high groups were consistent with the classic pathological manifestations of the disease. (4) The LPS-low group, LPS-mid group, and LPS-high group had patchy cotton wool like shadows on CT scans of the lungs, accompanied by irregular density enhancement shadows. (5) The lung function and blood gas analysis structure of the LPS-low group, LPSmid group, and LPS-high group showed a downward trend, with the LPS-mid group and BLM group showing more consistent performance (P> 0. 05). (6) The total cell count and neutrophil count in the alveolar lavage fluid of rats in the LPS-low, LPS-mid, and LPS-high groups increased, while the mass concentration of TNF-α in the alveolar lavage fluid and IL-6 in the serum increased. Among them, the LPS-mid and BLM groups performed more consistently (P> 0. 05). (7) The LPS-low group, LPS-mid group, and LPS-high group showed an increase in HYP content and α-SMA expression in the lung tissue of rats. Among them, the LPS-mid group and BLM group showed more consistent performance (P> 0. 05). Conclusions　This method can successfully prepare a rat model of acute exacerbation of idiopathic pulmonary fibrosis. The optimal dosage of lipopolysaccharide is 5 mg/ mL, and the optimal observation time is the 31st day.

• Imiquimod combined with chronic unpredictable mild stress to establish a mouse model of alopecia areata

  LYU Shuying, QU Baoquan, LIN Wenjun, YANG Dingquan

  2023,31(7):846-852, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 002

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  Objective 　To establish an imiquimod compound chronic unpredictable mild stress ( CUMS) C57BL/6J mouse model of alopecia areata (AA). Methods 　Thirty female C57BL/6J mice aged 5 ~ 7 weeks were randomly divided into three groups of 10 mice each: control, IMQ, and CUMS (imiquimod combined with CUMS) groups. CUMS was administered to the CUMS group on days 1 ~ 21, whereas IMQ and CUMS groups were administered equal amounts of imiquimod cream topically at the same site on days 14 ~ 21. On day 21, overall and trichoscopic photographs of mice were taken, behavioral tests were performed, and skin lesions and peripheral blood were collected. CD4P>+P> and CD8P>+P> T cell infiltration into hair follicles was observed by immunohistochemical staining. Differentiation of Th1/ Th2 and Th17/ Treg cells from peripheral blood T lymphocyte subsets was detected by flow cytometry. Results 　Compared with blank and imiquimod groups, C57BL/6J mice in the CUMS group showed significant localized patchy hair loss, and trichoscopic photographs showed broken hair and exclamation mark-like hairs. The distance moved, number of times standing upright, and number of times entering the central area in the open field test were significantly reduced (P< 0. 05). Moreover, the rest time in the forced swim test was significantly increased (P< 0. 05). These data suggested that the mice were in an anxious and depressed state. Compared with blank and imiquimod groups, CUMS group mice had significant CD4P>+P> and CD8P>+P> T cells in skin lesions around hair follicles and in the hair follicle bulb. Flow cytometry showed that Th1 levels were significantly higher (P< 0. 01), Th2 levels were significantly lower (P< 0. 05), Th17 levels were significantly higher (P< 0. 05), the Th1/ Th2 ratio was significantly higher (P< 0. 001), and the Th17/ Treg ratio showed an upward trend in the CUMS group. Conclusions 　The C57BL/6J mouse model established by topical imiquimod combined with CUMS essentially simulates human AA manifestations. This method highlights the psychosomatic factors in AA pathogenesis, and to some extent, conforms to liver depression and spleen deficiency syndromes in TCM, providing a cultivation-friendly and more cost-effective modeling method for basic research of AA.

• Mechanism of Zhenwu Decoction in improving renal inflammatory injury in diabetes with spleen-kidney yang deficiency based on NLRP3/ ASC / Caspase-1 pathway

  ZHAO Zhe, CHEN Guangshun, BAI Min, JIN Yuqiu, TIAN Mengyuan, ZHANG Yanying, LIU Zhenhua, SONG Bing

  2023,31(7):853-863, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 003

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  Objective　To study the effect and possible mechanism of Zhenwu Decoction on renal inflammatory injury in mice with spleen-kidney yang deficiency-type diabetic nephropathy. Methods　Mice (db/ m mice) were treated with rhubarb solution and hydrocortisone to induce a db/ db mouse spleen and kidney yang deficiency syndrome model. Mice in the blank control group were untreated. After successful modeling, the db/ db mice were divided randomly into a model control group, irbesartan group (25 mg/ kg), and high-, medium-, and low-dose Zhenwu Decoction groups (33. 8, 16. 9, 8. 45 g/ kg, respectively) (n= 15 per group). Mice in all groups except the blank control and model control groups were given the corresponding drugs by gavage once a day for 8 weeks. Mice in the blank control and model control groups received the same volume of normal saline. Traditional Chinese medicine syndrome scores were measured in each group. Fasting blood glucose ( FBG), urinary creatinine ( Ucr), and 24 h urinary protein (24 h UTP) were measured. Testosterone (T), triiodothyronine (T3), tetraiodothyronine (T4), estradiol (E2), interleukin (IL)-1β, and IL-18 levels in renal tissues were measured by enzyme-linked immunosorbent assay. Histopathological changes in the kidneys were observed by hematoxylin/ eosin staining. NOD-like receptor thermal protein domain associated protein 3 ( NLRP3), Apoptosis-associated speckle-like protein(ASC), Cysteinyl aspartate specific proteinase-1(Caspase-1) mRNA and protein expression levels in renal tissues were detected by Real-time quantitative PCR ( RT-qPCR) and Western Blot. Results　Mice in the model control group showed symptoms of spleen-kidney yang deficiency, such as anorexia, fatigue, and decreased, loose stools compared with the blank control group, while FBG, 24 h UTP, IL-1β, IL-18, and E2 were significantly increased (P< 0. 05) and T, T3, T4, and Ucr were significantly decreased (P< 0. 05). Renal pathology showed glomerular hypertrophy, and glomerular mesangial and basal thickening. Protein and mRNA levels of NLRP3, ASC, and caspase-1 in renal tissue were significantly increased (P< 0. 05). In contrast, mice in the high-, medium-, and low-dose Zhenwu Decoction groups had increased body weight, activity, and stool molding compared with the model control group, as well as significantly increased levels of T, T3, T4, and Ucr (P< 0. 05) and significantly decreased levels of 24 h UTP, IL-1β, IL-18, and E2 (P< 0. 05). In addition, pathological damage to the renal tissue was significantly improved and the protein and mRNA expression levels of NLRP3, ASC, and Caspase-1 were significantly decreased in all treatment groups (P< 0. 05). Conclusions　Zhenwu Decoction can improve the general condition and renal function, and reduce the inflammatory reaction and renal pathological injury in db/ db mice with spleen-kidney yang deficiency, via a mechanism possibly related to inhibition of the NLRP3/ ASC/ Caspase-1 pathway.

• Neuroligin 4 is independent of neurexin in regulating synaptic development in Drosophila

  ZHANG Xinwang, GENG Junhua, LI Li, ZHANG Juan, PENG Zexu

  2023,31(7):864-870, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 004

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  Objective　To determine if the Drosophila synaptic adhesion molecule neuroligin 4 (DNlg4) regulates the development of the larval neuromuscular synapse by interacting with the classic neuroligin (Nlg)-presynaptic ligand molecule Drosophila neurexin (DNrx). Methods 　Immunofluorescence staining and confocal microscopy were used to examine the morphology of the neuromuscular junction (NMJ) in Thrid-instar larvae in wild-type(WT), dnlg4 mutant, dnrx mutant, and dnlg4,dnrx double-mutant Drosophila. The length of the synaptic branches and number of synaptic boutons were used as parameters to assess the developmental status of the NMJ in the different genotypes. We determined the relationship between DNlg4 and DNrx in regulating the development of the NMJ by comparing the developmental defects in the different genotypes. Results　Deletion of DNrx result ed in more severe developmental defects in NMJs than DNlg4 deletion, characterized by shorter synaptic branches and fewer boutons. Loss of DNlg4 further aggravated the NMJ defects caused by DNrx deletion. The expression of exogenous DNlg4 in motoneurons partially rescued the developmental defects of NMJs caused by loss of DNrx. No in vivo physical interaction between DNlg4 and DNrx was detected. Conclusions　DNlg4 and DNrx have synergistic effects on the positive regulation of synaptic development in Drosophila larvae, and DNlg4 regulates synaptic development in a DNrx-independent manner.

• Effect of Astragalus polysaccharides on HIF-1 and S100A8/ A9 protein expression in the pre-metastatic niche of lung tumors and lung metastasis

  LIU Zhaohua, WANG Yanjun, SHEN Ming, CHEN Yanwen, LI Yang, YANG Lingling, LIANG Qiankun, MING Haixia

  2023,31(7):871-879, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 005

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  Objective　To observe the effects of different concentrations of Astragalus polysaccharides (APS) on hypoxia-inducible factor (HIF)-1 and S100A8/ A9 protein expression in the lung pre-metastatic niche(PMN), and to investigate the targets of APS in lung PMNs and its molecular mechanisms in relation to lung tumor metastasis. Methods Ninety specific-pathogen-free C57BL/6J mice were used, of which 15 were set as the blank control group. A PMN model was constructed in the remaining 75 mice by tail vein injection of 1 × 106 luciferase-labeled Lewis lung cancer cells. These 75 mice were divided randomly into five groups (n = 15 per group): model, low-dose (APS 50 mg/ kg), medium-dose (APS 100 mg/ kg), high-dose (APS 200 mg/ kg), and fingolimod (FTY720, injected intraperitoneally 1 mg/ kg) groups. APS was administered by gavage at the respective prescribed dose once a day on the day after inoculation of tumor cells and FTY720 was administered once every 2 days. The effects of different concentrations of APS on HIF-1 and S100A8/ A9 proteins in the PMN was observed and lung metastasis was assessed by hematoxylin/ eosin (HE) staining. On day 14, five mice from each group were randomly selected and lung tissues were removed and multifunctional proteoglycans, fibronectin, and lysyl oxidase were detected by Western Blot and Real-time qvantitative PCR (RT-qPCR), and histopathological changes in the lung were observed by HE staining. Protein and gene expression levels of HIF-1 and S100A8/ A9 in lung tissues taken at 28 days were also detected by Western Blot and RT-qPCR. Mice were fasted but had access to water for 12 h before sampling. Results　HE staining revealed alveolar wall thickening and granulocyte infiltration with a few tumor metastases in lung tissues in the model group. Tumor metastatic foci were significantly reduced and the lung tissues tended to be normal in the high-dose and FTY720 groups compared with the model group. HIF-1, S100A8, and S100A9 protein and gene expression levels were significantly higher in the lungs of mice in the model groups compared with the blank group (P< 0. 05), according to Western Blot and RT-qPCR. In contrast, the above protein and gene expression levels were decreased in the FTY720 group and all APS groups compared with the model group (P< 0. 05). Conclusions APS can reduce lung metastasis of tumor cells by regulating the expression levels of HIF-1, S100A8 and S100A9 in the PMN of lung tumors.

• Induced pluripotent stem cell-derived smooth muscle cells improve wound healing in diabetic mice

  GAO Xixiang, GAO Mingjie, GU Yongquan, GUO Lianrui

  2023,31(7):880-887, DOI: 10. 3969 / j.issn.1005-4847. 2023. 02. 006

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  Objective　To study the ability of human pluripotent stem cell-derived smooth muscle cells (hiPSCSMCs) to improve wound healing in diabetic mice. Methods　hiPSC-SMCs, positive control adipose-derived stem cells (ADSCs), and negative control cell-free phosphate-buffered saline (PBS) were added to type I rat tail collagen to prepare stem cell or cell-free collagen scaffolds. The scaffolds were applied to splinted back wounds in diabetic nude mice. The wound was photographed and harvested at various time points, and immunohistochemical staining and western blot analysis were performed. Results 　Compared with the cell-free control group, hiPSC-SMCs had the same ability as ADSCs to promote wound healing in diabetic mice. The wound size was significantly reduced the day after surgery. Wounds in hiPSCSMC and ADSC groups had significantly more cell proliferation, α-SMA-positive cells, CD31-positive cells, VEGF-Apositive cells, and VEGF-A and PDGF expression. Conclusions　hiPSC-SMCs promote the expression of angiogenic and regenerative cytokines, and promote angiogenesis and cell proliferation, thereby promoting wound healing in diabetic mice.

• Effects of three Tiao-Bu Fei-Shen therapies on lung and intestinal inflammation indexes in rats with stable chronic obstructive pulmonary disease

  XUAN Yinshuang, LI Ya, BIAN Qingqing, MAO Jing, LI Xiaojun, LI Suyun

  2023,31(7):888-895, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 007

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  Objective　To investigate the effects of three Tiao-Bu Fei-Shen therapies on interleukin (IL)-6, IL-33, and interferon (IFN)-γ in the lung and intestines of rats with stable chronic obstructive pulmonary disease (COPD). Methods　Sixty Sprague-Dawley rats were divided randomly into blank (Control), COPD model (Model), Bufei Jianpi (BJ), Bufei Yishen (BY), Yiqi Zishen ( ZS), and aminophylline ( Am) groups. A stable COPD rat model was established by cigarette-smoke exposure combined with lipopolysaccharide nasal drip in the first 8 weeks. The model rats were given normal saline, Bufei Jianpi Formula, Bufei Yishen Formula, Yiqi Zishen Formula, or aminophylline by gavage for 4 weeks. Morphological changes in the lung and colon were observed by light microscopy, and IL-6, IL-33, and IFN-γ protein levels in lung and colon tissues were localized and analyzed semi-quantitatively by immunohistochemistry. Results　Rats in the model group had more inflammatory cells and inflammatory exudates around the bronchi and alveolar spaces compared with control rats, and also had more inflammatory cell infiltration in the colon mucosa and significantly increased levels of IL-6, IL-33, and IFN-γ in the lung and colon tissues (P< 0. 05, P< 0. 01). Bronchial and alveolar inflammatory cell infiltration and colonic mucosal inflammatory cells were decreased in all treatment groups compared with the model group. IL-33 and IFN-γ in the lung and colon and IL-6 in the colon were significantly decreased (P< 0. 05, P<0. 01), and IL-6 in the lung was significantly reduced in the BY, ZS, and Am groups (P< 0. 01). There were positive correlations between lung IL-6 and colon IL-6, lung IL-33 and colon IL-33, and lung IFN-γ and colon IFN-γ levels. Conclusions　The three tested Tiao-Bu Fei-Shen therapies can reduce intestinal dysfunction in COPD rats. The mechanism may be related to inhibition of the release of IL-6, IL-33, and IFN-γ in lung and colon tissues, and reducing the inflammatory reaction between the lung and intestine.

• Characteristics and application analysis of animal models of ulcerative colitis

  ZHOU Xinxin, LIU Xixi, REN Zhen, JIANG Xin, BAI Li, MIAO Mingsan

  2023,31(7):896-904, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 008

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  Objective　To summarize the modeling characteristics of animal models of ulcerative colitis (UC) and provide a reference to establish an ideal animal model of UC. Methods　We searched the China Knowledge Base for topics of “ulcerative colitis” and “animals”, screened the relevant literature on animal experiments of UC from January 2012 to July 2022, and constructed a database using Excel 2017. The research contents, animal strains, modeling method, and detection indexes were sorted to analyze the model characteristics and main application directions of UC animal models. Results　After comparative analysis, we found that SD rats (247 reports, 43. 03%) and Wistar rats (105 reports, 18. 29%) were the animal strain used for modeling, male (355 reports, 64. 43%) was the main sex, and TNBS-ethanol solution enema (231 reports, 39. 69%) and DSS-free drinking (225 reports, 38. 66%) were the most common modeling method for both drug efficacy verification and mechanistic studies. Among these tests, colon pathology (269 reports, 13. 63%), disease activity index (DAI) score (246 reports, 12. 46%), general condition (231 reports, 11. 70%) and serum biochemical indices (225 cases, 11. 40%) and colonic tissue protein expression (171 reports, 8. 66%) were predominant. Conclusions　UC animal experiments are often performed in male SD and Wistar rats, which are modeled by a TNBS-ethanol enema and DSS-free drinking method. These method ologies have the advantages of ease, a high model establishment rate, and low cost, combined with colon histopathology, DAI scores, general conditions, serum biochemical indexes, and Colonic tissue protein expression, which provide the basis for UC animal experiments.

• Influence and mechanism of elevated serum uric acid levels in rats in a high temperature-humidity environment

  CHENG Yaxin, LI Jia, LIU Mingyu, TAN Wenbin

  2023,31(7):905-912, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 009

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  Objective 　Clinical evidence suggests that the risk of hyperuricemia is increased under high temperature-humidity conditions. The current study aimed to explore this effect and the possible molecular mechanism responsible for the environmental effect on serum uric acid (SUA) levels, using a recently established hyperuricemia rat model. Methods　Hyperuricemia was induced in rats by potassium oxonate (PO group) or a high-purine diet (HPD group) using traditional chemical-induction method. The rats were also irradiated in a high temperature-humidity incubator (37℃, 80% humidity) for 1 h/ d to produce the high temperature-humidity group (HTH group) and high purine diet +high temperature-humidity group (HPD + HTH group). A control group (CON group) was also included. The experiment lasted for 12 weeks. Anal temperature and body weight were measured during daily irradiation, and blood samples were collected every 4 weeks to examine SUA and creatine levels in each group. After the experiment, the kidneys were removed and expression levels of ATP-binding cassette super family G2 ( ABCG2) and urate transporter 1 ( URAT1) were determined by Western Blot and immunohistochemistry. Results　The anal temperature and dehydration rate of rats in the HTH and HPD + HTH groups were significantly increased after irradiation in a high temperature-humidity incubator (P<0. 05). SUA levels were significantly higher in the HTH group compared with the CON and PO groups, and in the HPD +HTH compared with the HPD group (P< 0. 05). There was no significant difference in serum creatinine among the five groups after 12 weeks (P> 0. 05). Expression levels of the uric acid secretion protein ABCG2 were significantly lower in the HTH and HPD + HTH groups compared with the CON group, in the HTH group compared with the PO group, and in the HPD + HTH group compared with the HPD group, as shown by Western Blot (P< 0. 05). Expression levels of the urate transporter URAT1 were significantly higher in the HTH and HPD + HTH groups compared with the CON group, in the HTH group compared with the PO group, and the HPD + HTH group compared with the HPD group (P< 0. 05). Immunohistochemistry indicated that both ABCG2 and URAT1 were expressed in proximal convoluted tubule epithelial cells. ABCG2 expression levels were lower while URAT1 expression levels were higher in the HPD + HTH and HTH groups compared with the other groups (P< 0. 05). Conclusions　A high temperature-humidity environment can influence the secretion and reabsorption of uric acid by disrupting the function of the uric acid transporters ABCG2 and URAT1, which are located in the proximal tubules of the kidney. This can lead to increased SUA levels, potentially aggravating the occurrence and development of hyperuricemia.

• Development of a mouse model for hind limb ischemia

  ZHANG Yongkang, YIN Kangli, ZONG Yuan, LIU Jiarui, WANG Yuzhen, CAO Yemin

  2023,31(7):913-921, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 010

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  The mouse hind limb ischemic model is a classic model used to study peripheral arterial disease. Six modeling method have been used to date: arterial ligation, interventional embolization, photochemical embolization, chemical injury, physical injury, and ameroid constrictor. This article reviews the anatomy of the murine hind limb artery and unifies the names of the major branches of the hind limb. We also introduce the modeling and evaluation method used in the mouse hind limb ischemia model, and compare the differences, advantages, and disadvantages of the existing method. Notably, mouse strain, sex, age, and method of anesthesia may affect the model. This report thus provides a comprehensive review of the modeling method of the mouse hind limb ischemia model and provides a reference for researchers to help them to select appropriate models according to their research direction.

• Research progress in epigenetics of senescence of mesenchymal stem cells

  MENG Bo, YANG Sheng, PENG Qing, ZHAO Wenjie, ZHANG Yu, HU Man, LIU Xin, ZHANG Liang

  2023,31(7):922-927, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 011

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  Mesenchymal stem cells ( MSCs) are adult stem cells with self-replication and multi-directional differentiation abilities. MSCs can differentiate into various human tissues such as bone, cartilage, and muscle, and thus have broad clinical application prospects in the endogenous repair of human tissues. However, increased cell replication and aging mean that MSCs inevitably face the problem of senescence, which affects and limits their clinical application. To allow MSCs to be applied more effectively in basic and clinical research, it is necessary to study the mechanisms responsible for their senescence and develop strategies to prevent its occurrence. This report highlights the role of epigenetics in MSC senescence.

• Establishment and application of osteoporosis animal models

  LI Yanran, YAN Panpan, MIAO Yanyan, MIAO Mingsan

  2023,31(7):928-934, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 012

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  With the increasing age of the population, and a large amount of bone calcium loss, osteoporosis has become a major public health problem. Osteoporosis is a “silent disease”, with a high incidence, high disability, and high death rates, which seriously affect quality of life. There are many animal models of osteoporosis, but there is a lack of relevant TCM disease and syndrome factors. Therefore, it can be combined with models that are highly consistent with clinical practice to make it closer to clinical research. In this article, we systematically review the advantages and disadvantages of various method of osteoporosis modeling, the advantages and disadvantages of animal species selection, the time of modeling, the drugs selection, and the application of assessment indicators to provide a reference for the standardization and improvement of animal model research.

• Preparation of animal models of drug-induced liver injury

  ZHAO Shanmin, WANG Yun, LIU Chang, CUI Shufang

  2023,31(7):935-945, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 013

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  Drug-induced liver injury is one of the most common adverse clinical drug reactions, potentially resulting in acute liver failure or even death. Clinically however, there is still a lack of specific diagnostic and treatment method for this kind of injury. The construction of corresponding animal models is an important process to support in-depth mechanistic research and screening of effective diagnostic and treatment method. Numerous animal models of drug-induced liver injury have been established and are widely used, including liver injury models induced by non-steroidal antiinflammatory, anti-bacterial, anti-epileptic, and anti-thyroid drugs, with mice and rats being the most commonly used animals. In this report, we review the preparation method, modeling standards, and characteristics of these types of animal models in combination with recent literature reports, to provide references for the future construction of related models.

• Application and development of germ-free animals for gut microbiome research

  HU Yaqian, WANG Shanshan, ZHANG Tong, YUAN Jiali, NIU Haitao

  2023,31(7):946-954, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 014

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  In recent years, with the introduction of the concept of metagenomics, human metagenomics has also become a new approach to reveal the development and health of humankind. As the largest microflora in the human body, the gut microbiome has been found to play an important role in the normal physiological functions of the human body and the occurrence and development of diseases. The variety and quantity of gut microbiome are abundant. In studies of the gut microbiome, the application of germ-free animals makes the experiments more accurate and convenient. It is an ideal basic animal model, which is of great significance to the research of microecology. This review summarizes the current understanding of germ-free animals, the application of germ-free animals in experimental research, and the prospects of germ-free animal models to review the application and development of germ-free animals in research of the gut microbiome.

• Research status and prospect of animal models of alcoholic liver disease

  LIU Mengjia, LIAN Yiqi, LYU Yi

  2023,31(7):955-962, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 015

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  Alcoholic liver disease (ALD) is a broad-spectrum disease caused by long-term heavy drinking, including alcoholic fatty liver, hepatitis, liver fibrosis, cirrhosis, and liver cancer. With the development of research, we have a certain understanding of the pathogenesis of ALD, but clinical treatment of ALD remains very limited. An appropriate ALD animal model is of great significance to elucidate ALD pathogenesis by seeking effective therapeutic targets and evaluating the therapeutic effects of related drugs. This review discusses the current research and development status of ALD animal models, introduces the modeling ideas, characteristics, and limitations of related models, and reviews the relevant new modeling ideas to provide a reference for researchers to establish appropriate ALD animal models.

• Research progress on the effects of enriched environment on maternal separation cognitive dysfunction

  LI Lingyu, LI Jinling, LIAO Xiaoyu, LUO Wen, SUN Hongyan

  2023,31(7):963-968, DOI: 10. 3969 / j.issn.1005-4847. 2023. 07. 016

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  With the introduction and implementation of China’ s three-child policy, the productivity of elderly mothers in China has increased yearly. Advanced elderly mothers is prone to a variety of difficult and high-risk conditions during pregnancy and delivery, with a subsequent increase in the birth rate of high-risk neonates. High-risk neonates are treated and cared for in the neonatal intensive care unit after birth and separated from their mothers. Maternal separation impairs cognitive functions, but no effective care has been found in clinical care. Numerous animal experiments have shown that enriched environment can improve cognitive dysfunction caused by diseases such as alzheimer's disease, depression, and ischemic stroke, but there are few reports and disagreements about the role and mechanism of the enriched environment in the model of maternal separation. Therefore, we reviewed the research progress on the effects of an enriched environment on cognitive functions in rodent models of maternal separation and the mechanisms of action with oxidative stress, epigenetics, synaptic plasticity, and the hypothalamic-pituitary-adrenal axis to provide new ideas for the improvement and care of cognitive functions in high-risk neonates.

Volume 31,2023 Issue 7

• Analytical methodology of human umbilical cord mesenchymal stem cells in mouse tissues and their tissue distribution of NOG mice after single intravenous injection

  Chen Guoyu, Pan Ruolang, Ye Zhichao, Shi Yuhua, Gu Liqiang, Xia Lijuan, Lin Xiaobo, Zhang Qiang, Xu Shasha, Shao Jinjin, Zhang Lijiang

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  ABSTRACT: Objective To establish a quantitative PCR method for the analysis of human-derived SRY gene DNA in mouse tissues, and to study the tissue distribution of human umbilical cord mesenchymal stem cells in immunodeficient NOG mice after a single intravenous injection. Method A quantitative PCR method for the analysis of human SRY gene DNA in mouse tissues was established, and the methodological validation of standard curve and linear range, accuracy and precision, and stability was performed. Thirty-six NOG mice, one half of each sex, were given HUCMSCs 3.5?07 cells/kg by single intravenous injection, and six mice were anesthetized at 6 h, 12 h, 24 h, 72 h, 1 w and 2 w, respectively, and dissected after blood collection (EDTA anticoagulation). DNA was extracted from lung, kidney, heart, liver, brain, spinal cord, stomach, small intestine, fat, skin, spleen and testis (uterus and ovary), and the distribution of HUCMSCs in each tissue was determined by the validated method of quantitative PCR analysis of human-derived SRY gene in mouse tissues. In addition, 18 NOG mice, half males and half females, were divided into control group (6 mice) and treating group (12 mice), which were injected intravenously with 0.9% sodium chloride injection and HUCMSCs 3.5?07 cells/kg. The acute toxic reactions of mice were observed during the administration period, and four animals were dissected at 72 h, 2 w and 4 w after the administration to observe the gross organs, and the mitochondrial protein expression was detected by immunohistochemistry in paraffin sections of lung tissues to analyze the colonization of HUCMSCs in lung tissues. Results The established quantitative PCR method for human-derived SRY gene DNA in mouse tissues met the validation criteria for each index. After a single intravenous injection in NOG mice, HUCMSCs were mainly distributed in the lungs and bloodwithin 1w after administration, with higher concentrations in lung tissues than in blood, and the concentration of HUCMSCs in lung tissue and blood maintained relatively stable levels within 6h~24h and 6h~72h, respectively, and then decreased over time. The distribution of HUCMSCs was not measured in other tissues at all sampling points . The colonization results showed that HUCMSCs were detected in lungs 72h after intravenous injection, but not at 2w and 4w. No obvious acute toxicity was observed in NOG mice after single intravenous administration of HUCMSCs. Conclusion The established method for analyzing the distribution of HUCMSCs in mouse tissue is reliable and feasible. HUCMSCs were mainly distributed in lung and blood of NOG mice within 1w after single intravenous injection, and mainly colonized in lung tissue at 72h. The single intravenous administration of HUCMSCs has a good safety profile.

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• Progress of animal model of bleomycin-induced pulmonary fibrosis

  wangbo, songqinghua, tanghuimeng, liuyang, xieyang, tianyange

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  Pulmonary fibrosis (PF) is a progressive, interstitial fibrotic lung disease characterized by persistent scar formation in the lung parenchyma and a reduced quality of life and poor prognosis for patients. The pathogenesis of PF is unknown and there is a lack of effective therapeutic agents, and animal models are the main tool to explore the pathogenesis of the disease and to find effective therapeutic agents. A variety of factors can induce fibrosis formation, and PF models can be induced to different degrees according to known etiology. Among them, bleomycin-induced models are widely used because of their reproducibility and similarity between fibrosis pathology and clinical conditions, and their induction methods mainly include intratracheal drip, intratracheal nebulization, tail vein injection, intraperitoneal injection and transnasal inhalation, and they are classified into single dose and multiple doses according to the frequency of induction. Based on the relevant literature, this paper summarizes the characteristics of the PF model established by BLM with different induction frequencies and induction methods, and provides a basis for the application of this model.

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• Effects of Oral Probiotics on Gut Microbiota Structure in Subcutaneous Tumor of Colon Cancer Mice Based on 16S rRNA Sequencing Technology

  Zhang Shuling, Wang Junwei, Zuo Luyu, Hu Shiliang, Sun Junzhi, Wang Chun

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  Objective To investigate the effects of oral probiotics on gut microbiota diversity, colony structure, and intergroup differences in mice with subcutaneous colon cancer tumors, based on 16S rRNA sequencing technology. Method Twenty-four 6-week-old male BALB/c mice were divided randomly into normal control (NC, n=8), model (M, n=8), and probiotic+model groups (PM, n=8) after adaptive feeding for 1 week. Mice in the PM group were given 200 μL probiotic mixed solution (Bifidobacterium longum and Lactobacillus delbrueckii subsp. bulgaricus mixed lyophilized powder, 2×108 colony-forming units) by gavage three times/week for 7 weeks, while the M and PM groups received 200 μL normal saline. At 10 weeks old, 0.2 mL CT26.WT cell suspension (1×107/mL) was inoculated subcutaneously into the left hind limbs of M and PM mice, while NC mice were inoculated with 0.2 mL normal saline. The general condition of the mice and growth of subcutaneous tumors, and changes in the gut microbiota structure by 16S rRNA sequencing were monitored. Results The subcutaneous tumors of the M group were prominent, and the subcutaneous tumor volume and weight of the PM group were significantly reduced (P<0.05). Compared with NC group, Alpha diversity index was lower in the M group, and a significant difference of Beta diversity inter groups (P<0.01).And supplementation of probiotics had a certain effect on gut microbiota diversity in the M group. Compared with M group, the relative abundance of Bacteroidetes, Proteobacteria, Muribaculaceae, Bacteroides were higher in the PM group, while the relative abundance of Firmicutes, Desulfobacterota, Lachnospiraceae_NK4A136_group, Alistipes were lower in the PM group. LEfSe analysis showed that Muribaculaceae and Bacteroides in the PM group were different species with high abundance (LDA values >4). Conclusions Oral probiotics may improve the gut microbiota by increasing the relative abundance of beneficial Muribaculaceae and Bacteroides in subcutaneous tumors in mice with colon cancer.

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• Advances in the application of 5XFAD transgenic mice in Alzheimer's disease research

  liu yi duan, ye tian yuan

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  5×FAD mice (Transgenic mice with five familial Alzheimer's disease) are APP/PS1 transgenic mice carrying five familial gene mutations. With beta-amyloid precursor protein (amyloid precursor protein, APP) related to the mutation of K670N/M671L (Swedish), 1716 v (Florida) and V7171 (London), and the old element - 1 (early presenilin 1, PS1) were MI46L and L286. 5×FAD mice had A large amount of β-amyloid (Aβ) in the brain at 1.5 months of age, and neuritic plaques (NP) began to appear at 2 months of age. The pathological phenotypes of 5×FAD mice included amyloid plaque aggregation, neuronal loss, gliosis, and memory dysfunction.The biological characteristics of 5×FAD mice may involve changes in the formation of brain Aβ plaques, hyperphosphorylation of Tau protein, synaptic dysfunction, neuroinflammatory response, mitochondrial dysfunction, blood-brain barrier injury, neuronal injury, endoplasmic reticulum stress and eye lesions. As a classic animal model of Alzheimer's disease, 5×FAD transgenic mice can simulate the neuropathological process and behavioral manifestations of AD patients in the late stage, and are widely used in the pathogenesis of AD and the development of new drugs for AD. In this paper, the model construction, biological background, biological characteristics of 5×FAD transgenic mice and the development and application of AD prevention and treatment drugs were summarized and reviewed, in order to provide reference for the application of 5×FAD transgenic mice in AD research.

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• Effect of different sterilization methods on the nutritional composition of pig specific formula milk powder

  GUO ya-xi, Liuruixue, Duxiaopeng, Zhuhua

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  【Abstract】Objective Using different sterilization methods to sterilize pig specific formula milk powder, exploring the sterilization method and conditions that minimize the loss of nutritional components in formula milk powder. Method Pig-specific formula milk powder was divided into high-pressure sterilization and irradiation sterilization groups. Formula milk powder in the high-pressure group was sterilized using different sterilization conditions and that in the irradiation group was sterilized using different 60Co γ-radiation doses. The sterility and the nutritional contents of the sterilized formula milk powders were determined according to national standards. Results The sterility tests for both groups of formula milk powder were negative. Compared to control group, the crude protein contents were significantly lower in formula in the high-pressure group sterilized at 121℃ for 30 min and in the irradiation liquid group sterilized at 50 kGy (P < 0.01). The water, crude protein, and calcium contents were significantly lower (P < 0.001) in the irradiation group sterilized at 50 kGy. There was no significant difference in the valine, isoleucine, or leucine content under 50 kGy sterilization conditions in the irradiation sterilized group, but all amino acid contents were decreased in the high-pressure sterilization and irradiation sterilized liquid groups (P < 0.001). Analysis of trace elements showed an increased iron content (P < 0.001) in formula sterilized at 121℃ for 30 min in the high-pressure sterilization group, increased iron and potassium contents (P < 0.001) under 25 kGy sterilization conditions in the irradiation sterilization liquid group, and increased magnesium content (P < 0.01). The magnesium (P < 0.05) and sodium contents (P < 0.01) differed significantly in formula treated under 50 kGy sterilization conditions in the irradiation sterilized powder group. Vitamin E and Vitamin B2 contents were increased in formula sterilized at 121℃ for 30 min in the high-pressure sterilization group (P < 0.001), the Vitamin E content was increased (P < 0.05) and the Vitamin B2 content was decreased (P < 0.001) in formula sterilized under 50 kGy conditions in the irradiation sterilization liquid group, and the Vitamin E and Vitamin A contents were decreased in formula sterilized at 25 kGy in the irradiation sterilized powder group (P < 0.001). Conclusion Sterilization at 121℃ for 30 min resulted in the least loss of nutritional components in the high-pressure sterilization group, while irradiation sterilization resulted in the least loss of nutrients at a dose of 50 kGy. Comparing the two sterilization methods, irradiation of milk powder at 50 kGy resulted in the least loss of nutrient content.

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• Research progress on animal models of diminished ovarian reserve

  liang xiaolei

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  Diminished ovarian reserve (DOR) is associated with a reduced quantity and/or quality of retrieved oocytes, usually leading to low numbers of retrieved oocytes and poor reproductive outcomes. DOR may potentially progress to premature ovarian insufficiency and premature ovarian failure, which have adverse impacts on women’s health. There is currently no effective clinical treatment to rescue ovarian function. The limited availability of human ovarian tissues and medical ethics issues mean that animal models are crucial for improving our understanding of the molecular pathogenesis of DOR and identifying preventive and therapeutic targets. This review thus aims to summarize the techniques and strategies used to establish rodent models of DOR, to provide a reference for future studies.

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• Research progress of pig in biology as model animal

  wangyan, Xing Kai, Cao Yong Chun

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  Animal models of human diseases include experimental animals and related materials established during biomedical research, which in turn play a vital role in medical research. Pigs and humans are similar in terms of their anatomy, physiology, immunology, and genetics. Pigs are thus suitable model animals for biomedical research and have various advantages compared with other model animals. Recent advances in biotechnology, such as genetic engineering, have contributed to a rapid increase in the use of pig models for human disease research. In addition to serving as xenotransplant organ donors and as tools in drug-design studies, pigs can also be used as model animals to study human developmental processes, congenital diseases, and disease-response mechanisms, thus making important contributions to improving human health. This review considers the current status and future applications of pigs as research models for studies of human cardiovascular diseases, cancer, ophthalmology, craniofacial, musculoskeletal, and skin research, reproductive and fetal development, nutrition, microbiome research, brain and neurodegenerative diseases, diabetes, infectious diseases, and vaccine design, as well as for xenotransplantation.

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• Syndrome evaluation of hot flash model rats induced by bilateral oophorectomy and tamoxifen administration

  Xie hiana, Pan zhiqiang

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  【Abstract】Objective To explore the animal model of syndrome used in the study of hot flash phenomenon in women. Methods Twenty-four female SD rats were randomly divided into three groups: sham operation group, bilateral oophorectomy group and tamoxifen group, with 8 rats in each group. Two kinds of hot flash animal models were induced by bilateral oophorectomy and tamoxifen intragastory at 10 mg/kg/d, respectively. On the 14th and 28th days of modeling, the open field activity, anal temperature and body surface infrared thermogram of rats were detected. On the 29th day, the rats were killed, and the uterus was weighed and pathological sections were made. Blood estradiol and epinephrine were determined by ELISA. The gene expressions of adrenal sex hormone synthetase (Star, Cyp11a1, Cyp17a1, Cyp19a1, Por, Hsd3b2, Hsd17b1) and catecholamine substance synthetase (Th, Ddc, Dbh, Pnmt) in adrenal medulla were detected by RT-qPCR. Results Compared with sham operation group, the body weight of rats in bilateral ovariectomy group increased significantly (P < 0.01), while the body weight of tamoxifen group increased slowly. In the bilateral ovariectomies group, the maximum body surface temperature was significantly decreased on day 28 (P < 0.01), the difference between the maximum temperature and the minimum temperature in the abdomen was significantly increased on day 14 (P < 0.05), the difference between the maximum temperature and the minimum temperature in the back was significantly increased on day 28 (P < 0.01), and the open field activity of the rats was decreased (P < 0.01). The maximum body surface temperature of the tamoxifen group was significantly decreased (P < 0.01), but the open field activity of the rats was increased (P < 0.01). The uterine index of rats decreased significantly in both models (P < 0.01). Compared with sham operation group, E2 in bilateral oophorectomy group and tamoxifen group was significantly decreased (P < 0.01), NE and Epi were significantly decreased (P < 0.05), β-EP in bilateral oophorectomy group was also significantly decreased (P < 0.05). Compared with sham operation group, the adrenal Cyp11a1 gene expression in bilateral ovariectomized rats was significantly increased (P < 0.05), while the Cyp17a1 and Hsd17b1 gene expressions were significantly decreased (P < 0.05). The gene expressions of Star and Por in tamoxifen group were significantly increased (P < 0.01), while the gene expression of Cyp17a1 was significantly decreased (P < 0.01). Pnmt gene expression was significantly down-regulated in bilateral oophorectomy group (P < 0.01). conclusion Bilateral ovariectomized rats can be used for the study of perimenopausal hot flashes, whose syndromes are similar to those of kidney Yang deficiency and Yin deficiency in traditional Chinese medicine.

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• Transcriptomic analysis of C57BL/6N-Tg(1.28HBV)/Vst Hepatitis B virus transgenic mice

  li rongrong, sunxin, huangkai, zhaozhimin, pengyuan, liuchenghai

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  【Abstract】Objective To observe the characteristics of C57BL/6N-Tg (1.28mer HBV)/Vst transgenic Hepatitis B virus (HBV-Tg) mouse model and analyze the transcriptomic characteristics of HBV-Tg mouse model. Methods 10 male HBV-Tg mice were used as experimental group and 10 wild-type mice as control group. The level of HBV DNA, HBsAg, HBeAg in serum and the expression of HBsAg and HBcAg in liver tissue were used to evaluate the virological characteristics of the model mice. The levels of serum ALT, AST, HE, Sirius red staining and Hyp in liver tissue were detected to evaluate the degree of liver inflammation and fibrosis. Liver tissue samples from 3 mice in each group were randomly selected for RNA extraction for high-throughput transcriptome sequencing. The significantly expressed differential genes were obtained by R software analysis, the functional enrichment of differential genes was obtained by GO and KEGG analysis, and then the genes with significant differences were verified by real-time fluorescence quantitative PCR (qRT-PCR). Results Compared with normal group, ALT and AST levels in model group were increased, and ALT was more significant (P<0.05). HE staining of liver tissue in model group showed the enlargement of liver nucleus and swelling of some hepatocytes. The results of Sirius red staining showed that there was a small amount of collagen deposition in the sink area and interlobule of HBV transgenic group, which was in the shape of thin lines. A total of 1352 differential genes were obtained by screening conditions (logFC>2x and P<0.05), including 703 up-regulated genes and 649 down-regulated genes. KEGG analysis suggested that differential genes were mainly enriched in PPAR signaling pathway, retinol metabolism, fatty acid degradation and other pathways (P<0.05). Significantly up-regulated differential genes mainly included Cyp4a10, Cyp4a14, Acot1, Acot3, Ehhadh, etc. Significantly down-regulated genes included Adh4, dnajb11, hspa5, scn5a, apol10b, etc. The trend was consistent after qRT-PCR detection (P<0.05). Conclusions HBV-Tg mice have a tendency of spontaneous fibrosis.Transcriptomic analysis shows that the potential mechanism of CHB mainly involves PPAR signaling pathway, retinol metabolism,fatty acid degradation,drug metabolism and other pathways.

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• Research new progress in aging models of rodent animal

  LI Xuechan, HAN Le, WANG Xuewen, LIU Lijun, WANG Jing

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  Aging is a process of degenerative change that occurs as a result of time-related accumulation, associated with age-related diseases. Understanding the causes and mechanisms of aging and finding drugs that can effectively delay aging and prevent and cure age-related diseases currently present a great challenge for humans. Aging animal models thus represent an important tool in aging research, and various aging animal models have been created using different aging mechanisms. These different models having specific advantages and disadvantages, making them suitable for different research purposes. This review considers aging rodent models to provide information for aging research.

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• Construction and evaluation for chemotherapeutic phlebitis rats induced by vinorelbine through dorsalis pedis vein

  王, jihaijie

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  To establish and evaluate for chemotherapeutic phlebitis rats induced by vinorelbine through dorsalis pedis vein. Methods The rats were randomly divided into the control and model group. Rats injected 0.1ml normal saline through the dorsalis pedis vein of the hind limb served as the control. While the rats in model group were injected with different concentrations of vinorelbine (2-5mg/ml) as above. General observation was performed and the hind limb volume was measured daily to calculate the swelling rate for 7 consecutive days. Then the rats were killed to collect the dorsalis pedis vein, and the histological changes were observed by HE staining. The microstructure changes on the surface of the vascular endometrium were observed by scanning electron microscopy. Results Rats injected with 2-5 mg/ml vinorelbine via dorsalis pedis vein could significantly induce hind limb swelling. The swelling rate increased with increasing concentration, and the peak of each group is reached on 3rd day. On the 7th day, the phlebitis rate in the 2 mg/ml group was 50%, while in the 3 mg/ml group of 83.3%. The 4 mg/ml group and 5 mg/ml group were all sucessful with grade Ⅲ accounting for 66.7% and grade Ⅳ accounting for 83.3%, respectively. Histopathology showed inflammatory cell infiltration, wall thickening, lumen stenosis and thrombosis in the surrounding tissues of veins. Scanning electron microscopy also showed that the tight junction of venous endothelial cells were destroyed, and the surface of the vascular lining were rough that resulting in blood cells adhesion. Conclusion Rats injected with 0.1ml 3-5mg/ml vinorelbine through the dorsalis pedis vein could induce red, swollen and cord like veins in lesions. Inflammatory cells infiltration around the vein, thickened vein wall, lumen stenosis and thrombosis were seen. Also, the surface of the vein intima was rough and adhered to a large number of blood cells. All of those were consistent with clinical chemotherapeutic phlebitis in terms of symptoms and pathological structure.

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• Establishment and evaluation of anterior cervical discectomy fusion optimization model in small tailed Han sheep model

  DOU Xinyu, LIU YU, LIU Xiao, ZHU Bin, JIA Fei, WANG Linbang, SHEN Fei, LIU Xiaoguang

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  Objective Cervical disc herniation (CDH) is one of the common orthopaedic diseases. With the in-depth study of it and the development of cervical implants, the establishment of cervical fusion animal models has become an indispensable part. At present, there are few reported researches about the establishment and evaluation of cervical fusion animal models in China. The aim of this study is to provide a good animal model and evaluation scheme of implants for cervical spine-related research. Methods Small tailed Han sheep were chosen for anterior cervical discectomy fusion (ACDF) after modified operation and polyetheretherketone (PEEK) interbody fusion cage (Cage) (control group), 3D-printed Ti6Al4V Cage (experimental group 1) and new method Ti6Al4V Cage (experimental group 2) were implanted in different cervical segments (C2/3-C4/5) of each sheep respectively. After surgery, hematology and histopathological analysis were performed to evaluate the recovery of sheep and the biosafety of the materials. X-ray, CT, Micro-CT and quantitative analysis, hard tissue section staining and biomechanical tests were executed to assess the conditions of bone in-growth and bone fusion. Results The modified ACDF ovine model was established successfully. There was no significant difference in the important indexes of hematology (P< 0.05), and histopathological analysis showed there were no pathological changes such as inflammatory cell infiltration. The implants had a good biosafety..Furthermore, X-ray and CT showed the position of internal fixation and the interbody fusion were good. The results of Micro-CT and quantitative analysis at 3 and 6 months after operation showed that compared with PEEK Cage group, the bone volume/total volume and trabecular number in the new method Ti6Al4V Cage group and 3D-printed Ti6Al4V Cage group were significantly increased (all P < 0.01), while the trabecular spacing decreased significantly (all P < 0.01). Moreover, the new method Ti6Al4V Cage group had more bone growth (P < 0.01). Hard tissue section staining demonstrated that the pores of the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage had obvious bone growth and were relatively dense, and the combination was slightly better than that of PEEK Cage. Biomechanical evaluation indicated that compared with PEEK Cage, the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage reduced the range of cervical flexion-extention , lateral bending and axial rotation to a certain extent (all P < 0.05), at the same time enhanced the stability of cervical vertebra, and the new method Ti6Al4V Cage was more advantageous (all P < 0.05). Conclusions After the establishment of the modified ACDF ovine model, reasonable and effective assessment methods were used to demonstrate the rationality and effectiveness of the model, and good biosecurity of the Cages of the three materials. Compared with PEEK Cage, the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage had better performance in bone growth and bone fusion, which could enhance the stability of cervical vertebrae, and the new method Ti6Al4V Cage had more advantages.

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• Establishment and evaluation of a rat model of coronary microvascular disease with qi deficiency and blood stasis syndrome

  kangjing, yang li li, wang ziyan, You yue, shiyue, ma yanlei, meng hongxu, lilei

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  Objective To explore the establishment and evaluation of a rat model of coronary microvascular disease with Qi deficiency and blood stasis syndrome. Methods 45 male SD rats were randomly divided into sham operation group, coronary microvascular disease group and coronary microvascular qi deficiency and blood stasis syndrome group, with 15 rats in each group. The rats in the group of coronary microvascular disease with Qi deficiency and blood stasis syndrome were randomly deprived of sleep for 14 to 16 hours every day for 6 weeks, and the model of Qi deficiency syndrome was established. The animals in the sham operation group and the coronary microvascular disease group were fed normally for 6 weeks. Six weeks after the experiment, rats in the coronary microvascular disease group and coronary microvascular qi deficiency and blood stasis syndrome group were anesthetized, and then opened their chest and injected embolic microspheres (40~120μm) into the left ventricle,The animals in the sham operation group underwent thoracotomy without injection of embolic microspheres. On the 7th day after operation, relevant detection indicators were measured in each group. Results In the group of coronary microvascular disease, microsphere embolism was found in coronary microvascular, left ventricular ejection fraction and left ventricular shortening rate were significantly decreased, and the activities of creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH) were significantly increased. The heart function, hemorheology, myocardial enzyme index and the degree of myocardial cell damage in the coronary microvascular Qi deficiency and blood stasis syndrome group were significantly different from those in the sham operation group. Conclusion Sleep deprivation combined with intraventricular injection of embolic microsphere can successfully establish a rat model of coronary microvascular disease with qi deficiency and blood stasis syndrome, which is more suitable for the study of pathogenesis and mechanism of traditional Chinese medicine

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• The ferroptosis pathway mediated by GSH/GPx4 might play an important role in preventing hepatocyte peroxidative injury by aerobic exercise in elderly mice model

  Liu Yuqian, Yang Wenqian, Wang haitao

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  Objective To elucidate the role of Glutathione (GSH)/Glutathione peroxidase 4 (GPx4) -mediated ferroptosis pathway in preventing age-related hepatocyte peroxidation injury by aerobic exercise in mice, and to provide a new target for improving liver aging and metabolism disorders. Methods 20 SPF C57BL/6 male mice aged 52 weeks were randomly divided into the elderly control group, (EC) and the elderly exercise group (EE), with 10 mice in each group. The mice performed 16 w moderate intensity exercise with the incremental load (1~2 w 14 m/min, 3~4 w 15 m/min, 5~10 w 16 m/min, 11~16 w 17 m/min, 60 min/d, slope 0?. After perfusion of the ascending aorta, the lateral lobes of the liver were harvested for HE sections and ultrathin transmission electron microscope sections. The levels of 8-hydroxy-2 deoxyguanosine (8-OHdG), 4-Hydroxynonenal (4-HNE) in liver and serum interleukin-6 (IL-6) were detected by ELISA. Hepatic glycogen, triglyceride (TG), malondialdehyde (MDA), nicotinamide adenine dinucleotide phosphate (NADPH), and glutathione (GSH) were determined by colorimetry. Hepatic GPx4, glucose transporter (GLUT2) and NAD(P)H:quinone oxidoreductase 1(NQO1) and solute carrier protein 7 family member 11 (SLC7A11) were detected by Western blot. Results ① The oxidative damage of hepatocytes in elderly exercise mice were effectively delayed, and the normal structure of mitochondria and glycogen storage in hepatocytes were maintained. ② Compared with the elderly control group, the content of hepatic GSH and NADPH in the elderly exercise group were increased significantly (P<0.01). ③ Compared with the elderly control group, 8-OHdG, 4-HNE, MDA and non-heme iron in liver of the elderly exercise group were decreased significantly (P<0.01). ④ The expression of GPx4, NQO1 and SLC7A11 in the liver of the elderly exercise group were increased (P<0.01), while the expression of NOX2 was decreased (P<0.01). Conclusions The synthesis of GSH was increased in aged mice after aerobic exercise, which provided sufficient reaction substrates for GPx4, and GSH /GPx4 pathway was activated. The ferroptosis process was inhibited, which improved hepatocyte peroxidation damage caused by aging, and maintained the normal structure and physiological function of hepatocytes.

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• Role of monoamine oxidase A (MAOA) in prostate cancer progression

  CHEN Hanmu, LI Hui, ZHAO Jumei, SHIChanghong

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  Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes the oxidative deamination of monoamine neurotransmitters and dietary amines. It plays a crucial role in the pathogenesis, progress, and treatment of neuropsychiatric disorders. Recent studies have revealed that elevated expression of MAOA in prostate cancer (PCa) is closely associated with tumor progression and drives the heterogeneity of PCa. In this review, we summarize the role of MAOA in the development of PCa in different disease stages, including oncogenesis, development, invasion, metastasis, and drug resistance. We also discuss the involvement of MAOA in the tumor microenvironment and explore the potential utility of MAOA inhibitors. We further propose therapeutic strategies based on targeting MAOA in preclinical models to promote relevant clinical trials. This review aims to provide new potential therapeutic targets for the treatment of PCa.

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• Research progress on the application of zebrafish in breast cancer

  ZHANG Min, ZHANG Jingjing, NING Guozhu

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  Zebrafish xenograft model is of great importance in cancer modelling, especially xenografting of breast cancer. It facilitates real-time observation of tumor cell growth, metastasis, and interactions with the immune system, thus providing novel insights and experimental foundations for breast cancer treatment. Furthermore, the zebrafish xenograft model offers a valuable tool for high-throughput drug screening. This review provides an overview of how zebrafish xenograft model contribute in elucidating the underlying mechanisms in breast cancer development, as well as their use in screening anti-tumor drugs and conducting therapeutic research.

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• Prox-1 induces new lymphatic vessels to participate in the repair of spinal cord acupuncture injury

  chendandan, Meng fanwei

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  Objective To observe the distribution and characteristics of lymphatic vessels in normal and injured mouse spinal cord, and to explore whether lymphatic vessels participate in the repair of spinal cord injury. Methods Adult male Kunming mice were randomly divided into two groups (n=36), the normal group did not damage the spinal cord, the experimental group used acupuncture to prepare a spinal cord injury model. The distribution of lymphatic endothelial cells（LECs） in the spinal cord was detected by immunohistochemistry, and the expressions of lymphatic endothelial cell markers Prospero-related homobox-1 (Prox-1), lymphatic vessel endothelial cell hyaluronic acid receptor-1 (LYVE-1), flat foot protein (podoplanin) and the vascular endothelial cell marker CD34 in the spinal cord of normal and acupuncture-injured mice were observed. The spinal cord samples were subjected to immunofluorescence staining, and the source of new LECs was explored by observing the co-expression of LYVE-1/prox-1, LYVE-1/podoplanin and CD34/Prox-1. Results Lymphangoid structures are present in the spinal cord of normal adult mice, and are distributed in segments, walking laterally between white matter and gray matter; nascent lymphangoid-like structures appear in the spinal cord at the site of acupuncture injury, and Prox-1, podoplanin, LYVE-1, and CD34 are expressed simultaneously, and the expression of Prox-1 is time-ordered; after scarring at spinal cord injury, the nascent lymphangoid-like structure disappears. Conclusion: Segmental, transversely distributed lymphangoid-like structures are present in the spinal cord of normal adult mice, and the neonatal lymphangoid-like structures are involved in the reconstruction of spinal cord injury, and the nascent lymphatic endothelial cells may originate from the surrounding existing lymphatic vessels or vascular endothelial cells.

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• Establishment and Evaluation of Constipated Irritable Bowel Syndrome Model with Liver Depression Syndrome

  He Jiahui, He Jieying, Zhang Bairong, Zhang Shuidi, Wei Yuanjun, Yang Chaoyan, Chen Yanfen

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  Abstract:

  Objective Through single factor modeling method and multi factor combined modeling method, to prepare the rat models of liver stagnation syndrome constipation type irritable bowel syndrome (IBS-C), and provide ideal experimental animal models of IBS-C by comparing different indicators. Methods 42 sprague-dawley rats were randomly divided into blank group (Normal group), cold water gavage group (Cold group), restraint group (Restrain group), tail clipping group (Tail group), cold water gavage+restraint group (C+R group), and cold water gavage+tail clipping group (C+T group). During the modeling period, the body weight, food intake, water intake, and survival status of each group of rats, and open field behavior, fecal Bristol score, visceral sensitivity, and small intestine propulsion were observed. HE staining was used to observe the pathological changes of the rat colon, and ELISA method was used to detect the content of 5-HT and VIP in serum and colon. Results After modeling, the weight loss of rats in each model group decreased (P < 0.05 or P < 0.01), the amount of food and water decreased, and the content of 5-HT in serum of each model group increased. In the Cold group, the number of fecal particles and Bristol score decreased, while the content of 5-HT in the colon increased (P < 0.05 or P < 0.01); the total distance and average speed of the restraint group in the open field decreased (P < 0.01); the preference for sugar water in the Tail group decreased (P < 0.01); in the C+T group, the preference rate for sugar water, total open field distance, small intestine propulsion rate, defecation particles, and Bristol score decreased, while the content of 5-HT in the colon increased and the VIP content decreased (P < 0.05 or P < 0.01); the total distance, average speed, and VIP content in the colon of the C+R group decreased (P < 0.05). Except for the Tail group, all other model groups showed visceral hypersensitivity (P < 0.05 or P < 0.01) at various pressure values on the 7th and 14th day of modeling; pathological observation showed that no significant inflammatory cell infiltration or pathological changes were observed in each model group. Conclusions The combination of ice water gastric lavage and tail clamping method can successfully establish a rat model of liver depression syndrome in IBS-C, which maybe the first choice of five methods and lays the foundation for systematic and in-depth research on the mechanism of traditional Chinese medicine in preventing and treating IBS-C.

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• Research progress of candidate pathogenic genes related to depression

  Li Mengyao, Gao Feng, Zheng Fanfan, He Mengze, He Zhao, Li Youlei

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  Abstract:

  Depression is a complex mental disease with polygenic inheritance and a high incidence. Our understanding of the clinical manifestations and pathogenesis of depression has recently improved. Continuous progress in gene-editing technologies has increased the construction efficiency and reduced the cost of gene-knockout animals, leading to their increasing use in the fields of basic research and drug development for depression and providing a powerful tool for revealing the pathogenesis of depression. In this review, we summarize recent progress in understanding the roles and mechanisms of candidate genes in depression using knockout model mice.

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• Establishment of a novel composite rat model of chronic skeletal muscle injury

  lujingjing

  Abstract: (14) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  :The purpose of this study was to establish a new composite rat model of chronic skeletal muscle injury to explore the mechanisms and treatment methods of skeletal muscle injury. The model was established by combining vertical impact with prolonged forced sitting, and significant pathological changes and physiological dysfunction were observed. The model group rats had significantly lower open-field distances than the blank group, and HE staining showed muscle atrophy and rupture, as well as infiltration of inflammatory cells. The volcano plot in the sequencing results suggested significant differences in the Pf4 gene. The muscle tissue Go analysis of the model group rats showed upregulation of the oxygen binding and oxygen carrier activity pathways. KEGG analysis suggested that the chemokine signaling pathway and AMPK signaling pathway were activated. In conclusion, this study successfully established a composite model of skeletal muscle injury in rats, which can be used to study the pathological changes of skeletal muscle injury and evaluate the therapeutic efficacy of treatment methods, with practical application value.

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• A Brief Review of the cultivation and utilization of the rat resources

  Zhang Leying, Xu Wei, Zuo Qin

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  Abstract:

  Rats are one of the representative experimental animals since the genetic and environmental effects is comparatively easy to control and standardize. The rat is rather suitable as model for physiology, neuroethology, pathology and toxicology due to an approximately ten times larger body size compared to a mouse, offering several unique advantages in surgical procedures and clinical sampling of blood, tissues, etc. This paper review the cultivation and utilization history of the rat resources abroad to provide references of collecting, sharing and utilizing laboratory rat resources in our country.

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• NK cells and the application of their immunotherapy in tumor immunity

  wuxueliang

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  Abstract:

  Abstract Natural killer cells (NK) are important immune cells that recognize and eliminate virus-infected cells and tumor cells. NK cells play a crucial role in anti-tumor immunity by modulating the immune response through a variety of cytotoxic mechanisms and cytokine production. This article reviews the development and classification of NK cells, the mechanism of action, and the application of NK cell-based immunotherapy in tumor immunity, and clarifies the principle, status quo and development trend of NK cell-based anti-tumor immunotherapy, in order to provide ideas for the future research and development of NK cells.

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• Analysis of glaucoma animal models based on data mining

  yuanxifan, miaomingsan

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  Abstract:

  Objective ：To study the application of animal model of glaucoma and provide reference for the improvement of animal experimental methods and model. Methods Methods With“glaucoma ”and “animal models” as the main topics, literature related to animal models of glaucoma from 2012 to 2022 was collected from CNI and PubMed, and the species, gender, modeling methods and detection indexes of experimental animals were summarized, and the database was established for statistical analysis.Results A total of 400 articles conforming to the criteria were selected. Most of the experimental animals were C57BL / 6J mice, and most of them were male. Most of the modeling methods were anterior chamber injection induced type, transgenic type and laser photocoagulation induced type. The high frequency detection indicators mainly included intraocular pressure measurement, histopathology, western blot analysis and immunohistochemistry. Conclusions: at present, there are many methods to construct glaucoma animal models, but the intervention of related TCM factors is less. It is suggested to increase the glaucoma animal model combined with disease and syndrome. In this study, different animal models were evaluated by mining and analyzing the animal model experiments of glaucoma, and the mining contents provided references for the construction of animal models with high success rate of modeling, good reproducibility and high clinical coincidence, and provided ideas for the model improvement.

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• Exploring the protective effect of Helleborus thibetanus Franch alcohol extract on bone destruction in CIA rats based on OPG/RANK/RANKL signaling pathway

  shanwenting, liuxia

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  Abstract:

  【Abstract】 Objective To investigate the anti-inflammatory effect of Helleborus thibetanus Franchon on collagen induced arthritis (CIA) model rats and the effect on OPG/RANK/RANKL signaling pathway. METHODS Sixty female wistar rats were divided into (1) normal group (Control), (2) model group (Model), (3) positive drug group (methotrexate, MTX), (4) low-dose group, (5) medium-dose group, and (6) high-dose group. The CIA rat model was established by injecting bovine type II collagen into the tail root of rats using the collagen antibody induction method, and the drugs were administered by gavage after the model was successfully established. Normal group: 10 mL/(kg·d) of saline was given; model group: 10 mL/(kg·d) of saline was given; the positive drug group was given 2.0 mg/(kg·d) of MTX each time, three times a week; the iron chopsticks low, medium, and high dose groups were given 0.25g, 0.5g, 1.0g/(kg·d) each time; continuous gavage treatment for 25 day. Body mass of rats was recorded to observe the degree of foot swelling;rat ankle arthritis index score;micro-CT observation of histopathologic changes in ankle joint bone; hematoxylin-eosin (HE) staining for pathological changes in ankle joint bone tissue and synovial membrane of the rats;tests to observe changes in the number of osteoclasts were performed with anti-tartaric acid phosphatase (TRAP) ; PCR to detect the mRNA levels of osteoprotegerin (OPG), nuclear factor-κB receptor activator (RANK), RANK ligand (RANKL), tumor necrosis factor (TNF-α), and bone-forming protein 2 (BMP-2);Relative expression of OPG, RANK, RANKL, TNF-α and BMP-2 proteins were detected by protein immunoblotting (Western blot)Helleborus thibetanus Franchon on rats with rheumatoid arthritis and its potential pharmacological mechanism for osteoarthritic protection. Results The statistical results of the data showed that compared with the normal group, CIA rats showed slower growth of body mass (P<0.05), increased thickness of the plantar foot (P<0.05), narrowing of the joint cavity in the ankle joint, gnawing-like bone destruction of the bone tissues, and pathologic changes in the synovium,Such as inflammatory cell proliferation and abnormal synovial hyperplasia infiltration; Micro-CT results showed that: compared with the normal group, the model group, low and medium dose group, the ankle joint surface was uneven, incomplete in shape, and the ankle joint surface showed gnawing-like bone destruction, and the high-dose group had no significant changes in all indexes compared with the normal group; HE staining found that the ankle joint of the model group showed joint cavity narrowing, gnawing-like bone destruction, synovial tissue proliferation and inflammatory cell infiltration. The pathological changes such as destruction of bone tissue, synovial tissue hyperplasia and inflammatory cell infiltration were found in the ankle joint of rats in the model group; compared with the model group, bone tissue hyperplasia and inflammatory infiltration in the ankle joint of rats in the low, medium and high dose groups were significantly improved; TRAP staining observed that compared with the normal group, the model group had the largest number of osteoclasts, and the number of TRAP staining positive osteoclasts was reduced under the intervention of the low, medium and high dose groups; the results of qRT-PCR showed that, compared with the model group. The relative expression of OPG, BMP-2 mRNA was increased in the low, medium and high dose groups (P<0.05), and the relative expression of RANK, RANKL, and TNF-α mRNA was decreased in the low, medium, and high dose groups (P<0.05); the results of WB, compared with the model group, the relative expression of OPG, BMP-2 protein was increased in the low, medium, and high dose groups (P<0.05), and the relative expression of RANK, RANKL , and TNF-α protein relative expression decreased (P<0.05). Conclusion Helleborus thibetanus Franchon may alleviate the inflammatory response in vivo in RA rats by regulating the OPG/RANK/RANKL signaling pathway and exert its role as an anti-rheumatoid arthritis mechanism.

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• Biochemical characteristics of type 2 diabetes mellitus and its microvascular complications in animal models

  daihaoran, wangyue, wangxu, luijing, wuxiuhong

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  Abstract:

  Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia, which is seriously harmful to human health. Its prevalence rate is increasing throughout the country. Patients with chronic hyperglycemia develop severe microvascular complications such as diabetic nephropathy (DN), diabetic foot (DF), and diabetic retinopathy (DR). Nowadays, T2DM has become a public health problem in the world. How to effectively treat T2DM and prevent microvascular complications has become an important medical issue to be solved urgently. So far, animal models are still the main tools to study the pathophysiology and treatment of T2DM and its microvascular complications, and it is urgent to establish highly consistent animal models. Biochemical indicators are the most direct reflection of the physiological state and body health of animals, and are crucial in evaluating the success of models, often affecting the experimental results. At the same time, biochemical indexes are also important reference basis for disease diagnosis and drug intervention. In this study, the experimental data of the animal model of T2DM and its microvascular complications were summarized, and the biochemical indexes were analyzed, in order to provide theoretical reference for future related experiments.

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• Establishment and evaluation of mild to moderate closed traumatic brain injury mouse model

  buyuanjing, xudonggang

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  【Abstract】Objective To establish a stable mouse model of mild to moderate closed head injury and evaluate its effectiveness. Methods A total of 170 SPF-grade ICR mice were divided into the sham group(n=34) and the TBI group (n=136). The TBI group was subjected to brain injury by impact under conditions A-D, with 34 mice in each subgroup. After modeling, the score of mNss, fatigue rotating test, and Morris water maze test were used to assess the balance and learning ability of the mice; brain water content experiment, Evans blue experiment, HE staining, GFAP immunohistochemistry, and TUNEL immunofluorescence were used to analyze pathological changes in brain tissue. Results Compared with Sham group, mNss score and water maze escape latency were increased to varying degrees in TBI group, while stick stay time was decreased significantly, indicating that severe neurological dysfunction occurred in TBI group. Brain water content and evans blue content in brain tissue of TBI group mice were significantly higher than those in sham group, suggesting that they suffered from blood-brain barrier damage and brain edema. Histopathological examination showed that the neurons in the brain tissue of the TBI group showed obvious degeneration and contraction, the astrocyte proliferation and the proportion of apoptotic cells increased significantly, and the damage degree increased with the increase of the weight of the blow. Comprehensive analysis revealed that a weight of 60 g or 80 g with a height of injury at 20 cm could simulate mild closed head injury in mice; while a weight of 100 g or 120 g could simulate moderate closed head injury in mice. Conclusion A stable mouse model of mild to moderate closed head injury was established based on the principle of free fall, which laid the foundation for studying the mechanism and treatment strategies for mmTBI.

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• Based on modified bilateral carotid artery ligation way to establish vascular dementia rat model and to investigate the changing rules of cerebral blood flow and its effects on angiogenesis related pr

  chen jie, tang xin, chen pan, xie ziwei, xie haihua, zhang hong, zou yinjie, tan jie

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  Abstract:

  【Abstract】 Objective Through the modified bilateral carotid artery ligation way to establish VD rat model to observe the changes of cerebral blood flow and the expression of angiogenic proteins. Methods 36 Sprague-Dawley male rats were randomized into sham group（n=18）and model group（n=18）. In the sham group, only the bilateral carotid artery was isolated without ligation, while in the model group, bilateral carotid artery were ligated to establish VD model. Morris water maze behavior test was applied before and 14 days after modeling, the variation of cerebral blood flow was detected by laser speckle contrast imaging. The protein expressions of HIF-1α, VEGF and HO-1 were detected by Western Blotting and the contents of IL-4 and IL-10 were detected by ELISA. Results 14 days after modeling,the escape latency was significantly prolonged and the frequency of crossing the platform had significant decrease for model group as compared with the sham group (P < 0.05). 2 hours,3 days,7 days after modeling, the cerebral blood flow of the model group was significantly lower than that of the sham group (P < 0.05). 14 and 21 days after modeling, there was no significant difference in cerebral blood flow between the sham group and model group (P > 0.05).In the model group, cerebral blood flow decreased to a minimum at 2 hours after modeling (P < 0.05), and then began to recover. The peak of recovery occurred at 3 to 7 days after modeling, and returned to the level before modeling on the 14th day after modeling.At day 21 postoperatively, the expression of HIF-1α, VEGF and HO-1 proteins in hippocampus of the model group were increased remarkably (P < 0.05)and the contents of IL-4 and IL-10 in serum of the model group were significantly rose in comparison with sham group(P < 0.05). Conclusion The variation of cerebral blood flow in VD rats model establish by the modified bilateral carotid artery ligation way showed a certain time rule.At day 21 postoperatively, HIF-1α, VEGF and HO-1 in hippocampus increased significantly, accompanied by increased levels IL-4 and IL-10.

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• Preliminary study on the mechanism of infertility in female SD rats with spontaneous dwarfism

  long hong, Huo Chunmao, Li Kang, Bao FengYun, Qin TingYang, Zhao YuJia, Zhang ShiBin

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  Abstract:

  Objective To investigate the causes of infertility and its pathogenic mechanism in female SD rats with spontaneous dwarfism (short stature rat, SSR）.Methods Adult wild-type and SSR female SD rats were used for the study. Vaginal smear was used to observe the changes of motile cycle; ovulation promotion was compared using the simultaneous oestrus supernumerary ovulation method; ovarian and uterine weight and body weight, ovarian and uterine indices were measured; AMH, E2, FSH, LH, FSH/LH levels in serum were measured; transcriptomic sequencing of ovarian tissues will be performed to analyze gene expression differences.Results There were no abnormalities in the estrous cycle of SSR female rats., the body weight of SSR female rats was significantly lower than that of wild type, and their ovarian index and uterine index were significantly higher than that of wild type. The mean number of ovulation was significantly higher in wild-type SD rats than in SSR female infertile rats (p<0.001); serum AMH (p<0.01) and E2 (p<0.05) levels were significantly higher in wild-type SD rats than in SSR female infertile rats, and serum FSH (p<0.01), LH (p<0.01) and FSH/LH (p<0.05) The levels of FSH, LH and FSH/LH (p<0.05) were significantly lower in SSR infertile females than in SSR infertile rats, while PROG was not significant; transcriptome sequencing yielded 250 differentially expressed genes, including 190 up-regulated genes and 60 down-regulated genes. p53 signaling pathway and cytokine-cytokine receptor interaction. The MCC, MNC, EPC and Degree calculations of CytoHubba plug-in were used to screen the top 10 significant nodes, respectively, and the intersection was taken to finally obtain 9 Hub genes, namely Cxcl1, Cxcl2, Il1a, Il1b, Cd80, Mmp13, Mmp8, Fgf3 and Ptgs2.Conclusions Infertility in SSR female rats may be related to decreased ovarian reserve function and poor ovarian response. At the same time, Cxcl1, Cxcl2, Il1a, Il1b, Cd80, Mmp13, Mmp8, Fgf3, and Ptgs2 were screened to be associated with infertility, laying a theoretical foundation for further exploration of infertility mechanisms.

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• Research progress on the effects of different ketogenic diets on skeletal muscle performance and fatigue recovery

  Li tingting, ZHANG Hui, ZHANG Mingchen, WANG Hongying, ZHANG Pingping, WANG Xiaowen, SUN Zhongguang

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  Abstract:

  Objective: To summarize the effects of ketogenic diet on sports performance and fatigue recovery of animals and human beings, so as to provide a diet plan for competitive sports and rehabilitation training. Methods: Database PubMed, Web of Science, Embase and CNKI, VIP, WANFANG, CBM were selected. With "(ketogenic diet) and (athletic performance) or (exercise fatigue recovery)"as the retrieval formula, the retrieval period is not limited, and according to the inclusion criteria and exclusion criteria, 42 related literatures were finally included. Results: Ketogenic diet can increase blood ketone, provide energy for skeletal muscle, and play a certain regulatory role in skeletal muscle performance and fatigue recovery. ①Ketogenic diet transforms muscle fiber Ⅱb into Ⅱa through axonal germination and nerve reinnervation, improves the quality and function of mitochondria of fast muscle, and increases histone acetyltransferase to enhance skeletal muscle strength; ②Ketogenic diet uses ketone bodies to provide energy, which can reduce glycolysis and improve the ability of fatty acid oxidation in slow muscles to improve skeletal exercise endurance; ③Ketogenic diet can reduce endoplasmic reticulum stress, oxidative stress and inflammatory reaction of skeletal muscle, protect the body from injury, reduce the consumption of muscle glycogen and the accumulation of lactic acid, relieve fatigue after exercise and promote fatigue recovery. Conclusion: Ketogenic diet has low negative effects on the body, can improve the sports performance and fatigue recovery of animals, plays a maintenance role in humans, and can be used as a diet scheme in competitive sports and rehabilitation training.

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• Advances in the Application of Cortisol in Evaluating Stress in Dogs

  SUN Ning, FU Jialin, XU Shu, YU Xi, SHUI Yingyi, ZHU Qiwen

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  In recent years, cortisol had been used as a biomarker to assess stress in dogs. In order to evaluate the welfare of dogs,we reviewed the cortisol levels and changes in dogs under various stress and explored the influential factors which could relieve stress according to the variation law of cortisol levels ,so?as?to improve the measures to reduce stress in dogs. It is recommended to apply cortisol measurement and behavioral observation comprehensively to evaluate stress in dogs more accurately.

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• Mouse and monkey animal models for SARS-CoV-2 infection and pathology

  Dong E, ZhangBo, ChenTingwei, Li-Xiaozhuo, Li-Tianqing

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  Abstract:

  As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread globally, its genome undergoes ongoing mutations and evolutions, giving rise to different strains such as α, β, γ, δ, etc. Therefore, continuously development of drugs and vaccines targeting different strains becomes pivotal in addressing the COVID-19 pandemic. Constructing animal models of SARS-CoV-2 not only enables studying the pathogenesis of the virus but also stands as a crucial means for evaluating the efficacy of drugs and vaccines related to SARS-CoV-2. However, commonly used animal models such as mice exhibit limited susceptibility to wild-type SARS-CoV-2, underscoring the urgent need for animal models that can be infected with the novel coronavirus and better simulating human pathological and physiological conditions. This review summarizes the animal models used for studying SARS-CoV-2 infection and transmission, as well as their progress in characterizing the viral immunopathology.

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• The improvement of the preparation method for type II cardiorenal syndrome rat model

  Liu Qian, Wang Xin Ting, Cheng Pei Pei, Rong Jing Feng, Yang Tian Shu, Zhou Hua

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  Abstract:

  Objective To establish an improved type II cardio-renal syndrome rat model and evaluate it. Methods Twenty male SD rats were randomly divided into the sham group and the model group，with 7 rats in the sham group and 13 rats in the model group. The model group used the method of squeezing the heart under a small animal anesthesia machine to permanently ligate the left anterior descending branch of the coronary artery to cause myocardial infarction. One week later，unilateral nephrectomy (right nephrectomy) was performed. Two groups of rats underwent cardiac echocardiography，pathological staining，and blood and urine tests three weeks after right nephrectomy to verify the establishment of the model. Results Compared with the sham group，the cardiac function detected by echocardiography and the endogenous creatinine clearance rate in the model group rats significantly decreased (P<0.01)，the level of brain natriuretic peptide，blood creatinine, urea nitrogen，and 24-hour urine protein in the model group significantly increased (P<0.01). HE staining revealed disordered myocardial arrangement，atrophy of glomerulus，and infiltration of inflammatory cells in the model group rats. Picric acid Sirius red staining showed a significant increase in myocardial collagen fibers，irregular arrangement of renal tubules，and a large amount of collagen deposition in the model group rats. The positive staining area ratio was significantly increased (P<0.01). Conclusions This improved modeling method can provide a type II cardio-renal syndrome rat model with simple operation，minimal surgical trauma，and low mortality rate. This model simulates the early onset of cardiac and renal function damage and pathological changes in type II CRS，laying the foundation for systematic and in-depth research on the pathogenesis and pharmacological mechanism of type II cardio-renal syndrome.

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• Model construction and progress of focused gene therapy for dilated cardiomyopathy

  chenyulin, zhaoxinke

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  【Abstract】 Dilated cardiomyopathy is one of the main diseases causing heart failure, and there is etiological heterogeneity. Nearly 1/4 of the patients with dilated cardiomyopathy are related to genetics, and ventricular dilation and myocardial systolic dysfunction are the main characteristics of the disease.LMNA mutation is an important cause of hereditary dilated cardiomyopathy, and arrhythmia is an important clinical manifestation of hereditary dilated cardiomyopathy with LMNA mutation.In recent years, the construction and intervention of rodent dilated cardiomyopathy model based on the focused gene therapy of mice with C57/B6 genetic background has been a focus of research, and some important conclusions have been drawn from the construction of large animal models of dogs and pigs. However, large animals, especially non-human primates, are still more close to human models.At present, dilated cardiomyopathy is not involved in the heart disease model of non-human primates. Therefore, this paper reviews the studies on the rodent and large animal models of dilated cardiomyopathy at the genetic level, and also proposes the idea of developing a non-human primate dilated cardiomyopathy model based on the current research.It provides a new idea to study the pathogenesis and clinical treatment in the future.

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• Study on the pathogenesis of hyperlipidemia rats under different dietary conditions based on intestinal flora and short-chain fatty acid metabolism

  yangzongtong, SUN Tiefeng, lixiaojing, xudongchuan, yuanmin, jinguangqian, wangwenhui

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  Abstract:

  Objective The purpose of this study was to compare the changes of intestinal flora and the characteristics of short-chain fatty acid metabolism in hyperlipidemic rats induced by two different high-fat diets, and to explore the possible microscopic mechanism of hyperlipidemia from the point of view of host-intestinal flora-metabolism. Methods SPF SD rats were divided into two groups: (1) normal diet group (CG group), fed with high fat diet group (HFD1 group), fed with high fat diet group (HFD1 group), and fed with high fat diet group (HFD2 group). Rats were fed with 80g high fat diet and unlimited maintenance diet.燗fter 8 weeks, the levels of serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured, and the pathological changes of liver tissue and perirenal fat were observed by hematoxylin-eosin (HE) staining.燭he contents of colon were taken for 16s rRNA high-throughput sequencing to observe the changes of the structure and function of intestinal flora and the content of short-chain fatty acids in colon contents. Result Compared with CG group, food intake decreased and body weight increased in HFD1 group and HFD2 group, serum TC, TG and LDL-C increased significantly, liver tissue showed obvious steatosis and perirenal fat showed inflammatory lesions. After high-fat intervention, the relative abundance of intestinal microflora in rats changed significantly and there were gender differences, in which the relative abundance of Lactobacillus decreased significantly, and the structure and function of Lactobacillus decreased significantly, including total short-chain fatty acids, acetic acid, butyric acid and isobutyric acid. Conclusion The two kinds of high-fat diet can cause hyperlipidemia in rats, and the pathogenesis is basically the same, which is related to lipid metabolism and intestinal flora disorder. Daily restriction of a certain amount of high-fat diet can not only reduce the effect of high-fat diet on rat appetite, but also improve the stability of rat hyperlipidemia model preparation.

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• Effects of bear bile powder on promotion stage of early hepatocarcinogenesis in SD rats

  dongrui, zhangmei, hongzexuan, tangqian, zouxinyu, jiaguiyang, niyuanping, Shibutani Makoto, jinmeilan

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  Abstract:

  Objective Bear bile powder (BBP), a natural Traditional Chinese medicine (TCM), has antioxidant and anticancer effects. To clarify the modification effect of bear bile powder (BBP) on early period of hepatocarcinoma formation, we conducted an anticancer efficacy experiment using short-term carcinogenesis bioassay models. Method Forty 5-week-old male SD rats were divided randomly into the following 4 groups with 10 animals per group: DEN alone, DEN+PBO, DEN+PBO+BBP-L (200mg/kg BBP), DEN+PBO+BBP-H (400mg/kg BBP). All rats were injected intraperitoneally with 200 mg/kg N-diethylnitrosamine (DEN) and three groups given a diet containing 0.5% piperonyl butoxide (PBO). In addition, the rats of last two groups were orally administered 200 or 400 mg/kg BBP for 8 weeks. Results The relative and absolute liver weights in PBO-treated groups significantly increased compared to DEN alone group. However, the number and area of GST-P+ foci were significantly decreased in only DEN+PBO+BBP-L group compared to DEN+PBO group. In addition, the Ki-67+ cell ratio which are significantly increased by DEN and PBO were significantly decreased after treatment with BBP in both BBP-treated groups. Interestingly, the mRNA levels of Ccne1, Cdkn1b related to cell cycle Caspase 8 and Caspase 9 related to apoptosis were significantly increased only in the BBP-H group. However, these changes were not observed in the BBP-L group. Conclusion These results indicated that BBP has a suppressive effect in the early period of hepatocarcinoma formation, leading to the inhibition of preneoplastic lesions. In addition, these results suggested that the suppression mechanism of BBP is strongly involved in the inhibition of cell proliferation activity and induction of apoptosis. Furthermore, that a high dose of BBP may influence BBP’s inhibitory effect on the preneoplastic lesions.

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• Progress in the study of animal models of systemic juvenile idiopathic arthritis and macrophage activation syndrome

  Li Feng Ming, Tang Xue Mei

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  Systemic juvenile idiopathic arthritis (sJIA) is the most frequent rheumatic disease complicated by macrophage activation syndrome (MAS), which can be life-threatening in children. Current experimental animal models show only some of the characteristics of sJIA and MAS, and there is no perfect animal model that can replicate the whole process of sJIA and MAS. This article reviews the clinical features, advantages and shortcomings of these models, with the aim of providing ideas for exploring more representative animal models of sJIA and MAS.

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• Research hotspots and trends of Alzheimer's disease animal experiments: CiteSpace bibliometric analysis based on WOS database

  YANG Jia-hui, LIN Yin, CHEN Lai, luoxiaoquan

  Abstract: (39) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  Objective Alzheimer's disease (AD) brings a huge burden to patients and society. As an important means of studying AD, animal experiments provide a lot of scientific basis for clinical and scientific researchers. This paper adopts the method of bibliometric analysis to reveal the research status, hotspots and trends in the field of AD animal experiments. Methods We obtained publications in the field of AD animal experiments from 2018 to 2022 from the Web of Science Core Collection (WoSCC) database. We use the analysis software CiteSpace 6.2.R2 (Advanced) to analyze the general information and keywords of publications in this field. Results After analyzing 4015 articles included in this study from 2018 to 2022, it was found that the annual publication volume of papers has gradually increased. In terms of the number of articles, the United States, the University of California System, Saito T, and the International Journal of Molecular Science are the countries, institutions, authors, and journals with the largest number of articles. "Alzheimer's disease" had the highest frequency of occurrence, and "anxiety" had the highest central degree. Conclusion This field focuses on the study of pathogenesis and treatment methods, and the plasticity of entorhinal cortex, neurons and synapses is a hotspot of current research. Future research trends may mainly focus on Aβ plaque formation, tau hyperphosphorylation, neurofibrillary tangle accumulation, glial inflammation, and ultimately loss of proper neuroplasticity. This article visually analyzes the hotspots and trends of AD animal experiments to help researchers understand the latest situation.

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• Plantar injection of complete Freund's adjuvant induced behavioral and monoamine neurotransmitter changes in pain and depression comorbid model rats

  Yang Pu

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  Abstract:

  Objective To observe the effects of plantar injection of complete Freund's adjuvant (CFA) on pain-depressive behavior and changes in hippocampal monoamine neurotransmitters in rats, with the aim of establishing an animal model of related comorbidity. Methods 16 male, 8-week-old, SPF-grade healthy SD rats were randomly divided into a model group and control group with 8 rats in each group. In the model group, rats were anesthetized and injected with 100 μL of CFA in the left hind paw to induce the comorbid pain and depression model. In the control group, rats were injected with the same volume of saline. Pain thresholds were measured using the von Frey hair and thermal radiation instrument, and depressive-like behaviors were assessed using open field test (OFT), tail suspension test (TST), and forced swim test (FST). Enzyme-linked immunosorbent assay (ELISA) was used to measure the content of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in the rat hippocampal tissue, and histological changes in the hippocampal area were observed by hematoxylin-eosin (HE) staining. Results Compared with the control group, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in the model group were significantly decreased at 3, 7, and 14 days (P < 0.01); the total distance in the OFT was significantly reduced at 7 and 14 days (P < 0.01), and the time spent in the center zone was significantly decreased at 14 days (P < 0.01); the immobility time in the TST was significantly increased at 14 days (P < 0.01), and the immobility time in the FST was significantly increased at 7 and 14 days (P < 0.05, P < 0.01); the content of 5-HT, DA, and NE in the hippocampal tissue of the model group rats was significantly reduced compared with the control group (P < 0.01), and the hippocampal tissue in the model group showed pathological changes, including irregular neuronal shapes, loose and disordered arrangement, increased intercellular space, some unclear cell nuclei, and some neuronal contraction and apoptosis. Conclusion Injection of 100 μL of CFA in the footpad can cause pain hypersensitivity, depressive-like behavior, significant reduction of monoaminergic neurotransmitters in the hippocampus, and histological changes in the hippocampus, effectively simulating the manifestations of comorbid pain and depression, and is an experimental model for studying the pathological mechanisms of comorbid pain and depression.

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• Research Progress of Neurotransmitter Detection Technology in Living Brain

  Zhu Mingyu, Cui Lili, Chen Huan, Hou Hongwei, HU Qingyuan

  Abstract: (22) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  As an endogenous chemical substance, neurotransmitter plays a vital role in maintaining normal life activities of people. Abnormal levels of neurotransmitters can lead to physical, mental and some neurodegenerative diseases. However, the ultra-low concentration, complex chemical properties and release modes of neurotransmitters make their accurate detection in vivo a great challenge.In order to accurately monitor neurotransmitters in the brain and accurately understand the release kinetics of neurotransmitters, several commonly used methods for detecting neurotransmitters in vivo in the past five years and their research progress were reviewed.The basic principle and applicability of microdialysis, electrochemical sensor and fluorescence sensor are introduced in detail.

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• Research progress on animal models of acute exacerbation of various respiratory diseases induced by compound factors

  Qiu Zhiguang, SHAO Xuejie, LU Ruilong, TAN Yange, REN Zhouxin

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  Abstract:

  Based on the compound factors of clinical practice, some progress has been made in acute exacerbation models of respiratory diseases by "two-hit" method. In this review, the current research on acute exacerbation models of pulmonary fibrosis, chronic obstructive pulmonary disease and bronchial asthma constructed by compound factors is summarized. Furthermore, the characteristics and scope of application of each model are compared and analyzed in animal strain selection, model preparation methods and major histopathological changes, providing reference for researchers to further improve and perfect the model or rationally select the animal models.

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• Effect of miR-185-5p on proliferation, invasion and migration of mouse breast cancer PY8119 cells

  Liu Lu, Zhao Yanqiao, Wang Xiaona, Wang Kun, Yin Chonggao, Liu Qinghua, Li Hongli

  Abstract: (47) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  Object To investigate the effect of miR-185-5p on the proliferation, invasion and migration of mouse breast cancer PY8119 cells. Methods Mirna: miR-185-5p with significantly down-regulated expression in breast cancer was obtained by previous research group. The sequence of miR-185-5p gene from human and mouse was consistent by NCBI. The effects of overexpression and knockdown of miR-185-5p on the proliferation of PY8119 cells were detected by EdU proliferation experiment. The effects of overexpression and knockdown of miR-185-5p on the invasion ability of PY8119 cells were detected by Transwell invasion experiment. The effects of overexpression and knockdown of miR-185-5p on the migration ability of PY8119 cells were detected by scratch healing experiment. The effects of overexpression and knockdown of miR-185-5p on the apoptosis of PY8119 cells were detected by flow cytometry. The effect of overexpression of miR-185-5p on tumor proliferation in vivo was detected by C57BL/6 mouse subcutaneous tumor model. Lung metastasis of mice overexpressing miR-185-5p was observed by tail vein injection. Results The results of EdU proliferation experiment, Transwell invasion experiment, scratch healing experiment and flow cytometry showed that knocking down miR-185-5p significantly enhanced the proliferation, invasion and migration of PY8119 cells and inhibited apoptosis. Overexpression of miR-185-5p inhibited the proliferation, invasion and migration of PY8119 cells and promoted apoptosis. In vivo tumorigenesis experiment of C57BL/6 mice showed that overexpression of miR-185-5p slowed down the tumor growth rate in C57BL/6 mice. Lung metastasis experiment showed that overexpression of miR-185-5p inhibited the lung metastasis of C57BL/6 mice. Conclusion miR-185-5p can inhibit the proliferation, invasion and migration of mouse breast cancer PY8119 cells in vitro and in vivo as a tumor suppressor gene.

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• The welfare and untilization of experimental animals in tumor research

  zhanglingli

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  As an important intermediate link between in vitro cell experiments and clinical experiments, animal models are often preferred in the research of tumor mechanisms, prevention,diagnosis, and treatment. The results of animal experiments are directly related to animal welfare, and are important factors affecting the scientific and accurate results of the research. This article summarizes the relevant aspects of experimental animals involved in tumor research, including tumor animal models, animal welfare related to tumor models and humane endpoints.

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• Establishment and evaluation of rats model of rheumatoid arthritis with depression

  liyuanyuan, zhangbitao, fanpeijian, cuizilong, wangshaoxian

  Abstract: (28) HTML (0) PDF (0.00 ByteKB) (0)

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  Objective To prepare and evaluate the animal model of rheumatoid arthritis with depression (RAD). Methods Thirty-two rats were randomly divided into normal group (N group), depression group (D group), arthritis group (RA group) and model group (RAD group), with 8 rats in each group. The N group was fed normally, while the D group was fed solitary rearing for 1 week and chronic unpredictable mild stress (CUMS) for 3 weeks, RA group was induced by collagen-induced arthritis (CIA) to establish the arthritis model. In RAD group, RAD animal model was established on the basis of CIA animal model, meanwhile, adding 1 week solitary rearing and 3 weeks CUMS. Toe volume, arthrits index (AI), Synovial and ankle joint pathology, serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were used to evaluate whether the rat model of rheumatoid arthritis was successfully established; the depression status of rats was evaluated by measuring body weight, food intake, sugar water preference rate, open field behavior (total number of motion cells, number of standing uprights), serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), and pathological changes of hippocampus. The RAD animal model was successfully prepared if depression and rheumatoid arthritis were both tested in the rats. Results Compared with the N group, toe volume, AI score and the levels of IL-1β, IL-6 in serum of RA group and RAD group were significantly increased (P＜0.05 or P＜0.01), the joint space widened, synovial hyperplasia was obvious and extended to the joint cavity, and a large number of inflammatory cells were seen; in D group and RAD group, body weight, food intake, total number of motion cells, number of standing uprights and sugar water preference rate of rats were decreased to different degrees, and the levels of CRH, ACTH, CORT in serum were increased in different degrees (P＜0.05 or P＜0.01), the neuron cells arranged loosely, gap increased, the number decreased, accompanied by some nucleus pyknosis, dissolution, rupture, especially in the model group. Conclusion CIA combined with solitary rearing and CUMS can better simulate the changes in the external manifestations and internal indicators of RAD model animals, which can provide reference for the study of RAD disease animal models.

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• Study on the expression and methylation level of hippocampal Notch signaling pathway genes in perimenopausal depression rats

  shen jian ying, liang wen na, chen hui fang, zhang ling yuan, zhuang yuan ying, chen xiao yang, chen ya ru, xiao qiong qiong, yang min, gong lin, min li

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  Abstract:

  [Abstract] Objective To investigate the effect of perimenopausal depression on the expression of key genes of Notch signaling pathway and DNA methylation of its promoter in rat hippocampus from the perspective of DNA methylation of epigenetics. Methods 12-month-old female SD rats were randomly divided into control group and model group. Open field tests, sugar consumption tests, and forced swimming tests were used for behavioral evaluation. Real-time PCR was used to detect the expression of key genes of Notch signaling pathway in the hippocampal dentate gyrus of different groups. Bisulfite sequencing (BSP) was used to analyze methylation sites and methylation levels in the promoter region of key genes of the Notch signaling pathway. Results In perimenopausal depression rats, the horizontal and vertical scores of open field test and the rate of sugar water consumption decreased significantly; the expression of the key genes Jagged1, Notch1 and Hes5 on Notch signaling pathway was significantly down regulated in the hippocampus of perimenopausal depression rats (P＜0.01 or P＜0.05) ; among them, some methylation sites and methylation rates of Hes5 gene increased significantly, while the methylation sites and methylation rates of Jagged1 and Notch1 genes were not statistically significant (P>0.05) . Conclusion The expression of key genes of Notch1 signaling pathway in the hippocampal dentate gyrus of perimenopausal depression rats is significantly down regulated, and the down-regulation of Hes5 gene may be related to the increase of promoter DNA methylation level.

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• Quantitative inhalation method to established the model of chronic obstructive pulmonary disease in rats

  liuxuewu

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  Objective To compare the differences of chronic obstructive pulmonary disease (COPD) models induced by smoke inhalation through nose-mouth plus LPS or smoke exposure through wholebody plus LPS in rats, providing a new model for COPD model construction. Methods 90 male SD rats were randomly divided into normal control group, wholebody exposure group and nose-mouth inhalation group, with 30 rats/group. The wholebody exposure group were exposed in a homemade smoke box where smoke contacted with whole body of rats , and the smoke nose-mouth inhalation group were inhaled with somke via nose-mouth only in a "quantitative smoking device". Animals in both groups were exposed to smoke once a day for 60mins/time for 8 weeks, and LPS (1mg/kg) was injected through the trachea on day 1, 7, 15 and 21, respectively, to induce the COPD model. The quality control of smoke generated by quantitative smoking devices included the verification of the stability and uniformity of the concentration of smoke particles and the size distribution of smoke particles. At 4, 6 and 8 weeks of modeling period, pulmonary function examination, the content of inflammatory factor interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in alveolar lavage fluid and histopathological examination were performed to compare the differences between the two modeling methods. Results Quantitative smoking devices could produce smoke with stable concentrations of 1.1mg/L (counted as total particles) and 0.1mg/L (counted as nicotine), respectively, with a median mass particle size of 0.693μm (in nicotine) and a GSD of 1.463. Compared with the whole body exposure group, the indexes of pulmonary function FEV0.2/FVC and pulmonary compliance (Cdyn) in the nose-mouth inhalation group decreased more significantly, and the airway resistance (Penh) increased more significantly. The levels of IL-6 and TNF-α in the alveolar lavage fluid of rats in the nose-mouth inhalation group were significantly increased at 6 weeks after modeling, while those indexs in the wholebody exposure group were increased at 8 weeks after modeling. The lesion severity of bronchial inflammation after modeling was similar between the oral-nasal inhalation group and the wholebody exposure group, but the lesion severity of emphysema was more serious in the oral-nasal inhalation group (the time when appeared statistic difference: oral-nasal inhalation vs. wholebody exposure = 6 weeks of modeling vs. 8 weeks of modeling). The mean linear intercept (MLI) in the oral-nasal inhalation group increased significantly at 4-8 weeks of modeling, and the mean alveolar numbers (MAN) decreased significantly at 6-8 weeks of modeling. MLI increased significantly and MAN decreased significantly in the whole body exposure group after 8 weeks of modeling. In the oral-nasal inhalation group, significant abnormal changes were observed in pulmonary function indexes (FEV0.2/FVC, Cdyn, Penh), cytokine levels in Bronchoalveolar lavage fluid (IL-6, TNF-α), and alveolar histopathological changes (bronchial severity and emphysema pathological score, MLI, MAN) after modeling. However, the coefficient of variation (CV%) of each index was significantly lower than that of the whole body exposure group. Conclusion LPS (1mg/kg) endotracheal drip combined with smoke wholebody exposured or via oral-nasal inhalation both could establish a typical rat COPD model. Rats Inhalated smoke via oral-nasal could shorten the modeling period. The model could be completed after 6 weeks of continuous modeling, presenting typical symptoms of chronic obstructive pulmonary disease (pulmonary ventilation dysfunction, broncho-lung chronic inflammatory infiltration, accompanied by emphysema), and the difference between individual model animals were smaller (vs smoke exposure, CV% values were smaller).

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• Research progress of animal metacognition

  WANG WANNING, JIA NING

  Abstract: (21) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  It is widely believed that metacognition is a special cognitive capacity that only humans possess. A contentious debate in the field of comparative psychology is whether animals have metacognition. The exploration of this question has become an important way to uncover the phylogenetic roots of metacognition and to map the evolutionary history of higher cognitive functions in humans. This paper reviewed the main animal metacognition studies in the past 25 years. We summarize three common research paradigms and corresponding measures: the uncertainty monitoring paradigm, the information seeking paradigm, and the confidence judgment paradigm. Two opposing explanatory tendencies and their rationales are outlined in the field of animal metacognition research: the associative model and the metacognitive model. In response to the debate between the associative model and the metacognitive model, two future research orientations are proposed to improve the research paradigm to test the metacognitive model and the innovation theory to integrate the model.

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• Data mining based animal model for dilated cardiomyopathy

  gejunxi

  Abstract: (21) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  Objective To review the animal species, modelling methods and evaluation indexes of dilated cardiomyopathy (DCM) animal models at home and abroad, to provide suggestions for improving the success rate of modelling and establishing DCM animal models with Chinese medicine characteristics in the future, and to provide reference for the establishment of future DCM animal models. Methods The literature on animal models of dilated cardiomyopathy in the past 10 years was searched, and relevant reports were collected and summarized. Relevant parameters of experimental animals (species, sex, body weight, etc.), modelling methods, modelling cycles, positive control drug species and cycles, and model evaluation indexes were summarized and analysed. Results A total of 128 papers were included. Animal models of dilated cardiomyopathy were mostly prepared in SD rats and Wistar rats using the anthracycline adriamycin, with a cycle of 30 d

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• To investigate the effect of TMAO on lipid metabolism in spleen deficiency hyperlipemia rats and the intervention effect of Xiangsha Liujunzi decoction

  lengxue, 李阳

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  Objective To investigate the effect of TMAO, a metabolite of intestinal flora, on hepatic lipid metabolism in rats with splenic deficiency and hyperlipidemia, and to further explore the possible mechanism of Xiangsha Liujunzi Decoction in the intervention of hepatic lipid metabolism disorder. Methods SD rats were divided into: (1) Blank control group (group C), (2) blank control group DMB (group C D), DMB is TMAO inhibitor, (3) spleen deficiency hyperlipidemia group (PG group), (4) spleen deficiency hyperlipidemia DMB group (PG D), (5) Spleen deficiency hyperlipidemia Xiangsha Liujunzi Decoction group (PG XS group), Except group C and group C D, the other groups were constructed to establish spleen deficiency hyperlipidemia model (12 weeks of modeling) by combining excessive fatigue and high-fat diet. After model establishment, group C D and PG D were given 1%DMB in drinking water every day, and group PG XS was given Xiangsha Liujunzi decoction (11.34 g crude drug /kg/ day) every day. The other groups were given the same amount of normal saline. The blood lipid level of each group was detected by automatic biochemical method after 4 weeks of intragastric administration. The morphological changes of liver were observed by HE staining. The lipid deposition in the liver of each group was observed by oil red O method. Liver FFA, TG and TC were detected by ELISA. The plasma TMAO content was detected by LC-MS. The relative expression levels of PERK, FOXO1, SREBP-2, ABCA1 and miR-33 mRNA in liver were detected by qRT-PCR. The contents of SREBP-2 and ABCA1 gene protein in liver were detected by WB. Results (1) The content of TC, TG and LDL-C in serum of PG group was significantly higher than that in C group, and the content of HDL-C was significantly lower than that in C group; The contents of FFA, TG and TC in liver tissue of PG rats were significantly increased compared with those of C group. Compared with group C, lipid deposition in liver was aggravated and fat vacuoles were increased significantly. There was no difference between group C D and group C in the above indexes. Compared with the PG group, PG D and PG XS groups could significantly reduce the contents of TC, TG and LDL-C in serum, increase the content of HDL-C, reduce the contents of FFA, TG and TC in liver tissue, alleviate the phenomenon of lipid deposition in liver tissue and reduce liver vacuoles. There was no significant difference between PG D group and PG XS group. (2) Compared with group C, the plasma TMAO content of PG group was significantly increased, the liver PERK, FOXO1 and miR-33a mRNA expressions were significantly increased, and the liver SREBP-2 and ABCA1 mRNA and protein expressions were significantly decreased; There was no difference between group C D and group C in the above indexes. Compared with the PG group, PG D and PG XS groups could significantly reduce the plasma TMAO content, decrease the liver PERK, FOXO1 and miR-33a mRNA expressions, and increase the liver SREBP-2 and ABCA1 mRNA and protein expressions. There was no significant difference between PG D group and PG XS group. Conclusion TMAO may regulate the SREBP-2/miR-33a/ABCA1 signaling pathway through PERK/FOXO1 axis to cause liver lipid metabolism disorders in rats, and Xiangsha Liujunzi Decoction may inhibit liver lipid metabolism disorders by inhibiting TMAO content.

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• Study on the effect of Huanglian Jiedu Decoction on bile acid metabolism in SD rats based on serum metabolomics

  yangguangyong, duhaiyang, zhanggengxin, sugang, tuxiaohua, heguangzhi

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  Abstract:

  Objective To study the effect of Huanglian Jiedu Decoction(HLJD) on the physiological function of healthy SD rats through serum non-targeted metabolomics. Methods After 7 days of adaptive feeding, 24 rats were randomly divided into blank group (group N) and high-dose HLJD group (group H), medium-dose HLJD group (group M), and low-dose HLJD group (group L) with six rats per group. Group N was gavaged with physiological saline, and H, M, and L groups were gavaged with 6.250, 3.125, and 1.560 g/kg HLJD, respectively. Rats were gavaged with 1 mL twice per day for 21 d. Before collecting serum samples, fasting and water deprivation were performed for 12 h. After anesthesia, blood was collected from the abdominal aorta, and serum was separated. Changes in metabolic products in the serum were detected by Gas Chromatography Time-of-Flight Mass Spectrometry(GC-TOF-MS). Multivariate analysis by Orthogonal Projections to Latent Structures Discriminant Analysis(OPLS-DA) and univariate statistical methods were used to screen differential metabolites, and then metabolic pathway analysis was conducted using the Metabo Analyst platform. Results Compared with the group N, metabolic small molecules were significantly altered in the serum of group H, group M, and group L, which mainly included cholesterol, cholic acid, ribose, paclitaxel, cortisol, oleic acid, succinic acid, linolenic acid, acetic acid, and acetone alcohol (P < 0.05). Correlation analysis showed that HLJD significantly affected the metabolism of primary bile acids, alanine, aspartic acid, and glutamate in α-linolenic acid and glycerol phospholipid metabolism, and its in vivo effects may be related to the intake dose, providing a reference to further reveal the mechanism of HLJD in promoting bile acid metabolism. Conclusions HLJD promotes the production of primary bile acids in vivo and enhances the effects of the bile acid metabolic pathway.

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• The model of ulcerative colitis with spleen deficiency and dampness syndrome and the changes of T lymphocytes

  qiuping xiao, zhong youbao, yu songren, li shangshang, luo xiaoquan, chen liling, liu xuan

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  Abstract:

  Objective A mouse model of ulcerative colitis with spleen deficiency and dampness syndrome was established, and the role of T lymphocytes in this model was studied. Methods C57BL/6 mice were randomly divided equally into Control, FXY, 3% DSS, FXY+3% DSS and FXY+2% DSS groups. A mouse model of ulcerative colitis with spleen deficiency and dampness syndrome was established by DSS and senna leaf. At the end of moulding, HE staining was performed to observe structural changes in the colon tissue. Elisa assay was performed to detect the concentrations of inflammatory cytokines in the colon tissues. Flow cytometry was used to detect the levels of CD4/CD8 T lymphocytes, Th1/Th2, Th17/Treg cells. Results In the FXY group, the clinical symptoms of mice with spleen deficiency and dampness were mainly diarrhea, and mice with 3% DSS colitis mostly showed blood in stool, while mice with spleen deficiency and dampness colitis in the FXY+3%DSS and FXY+2%DSS groups mostly showed diarrhea and blood in stool, but the survival rate of mice in the FXY+3%DSS group was as low as 50%. Compared with the Control group, body weight, colon length and concentrations of anti-inflammatory cytokines IL-10 and TGF-β1 were significantly lower in the 3%DSS, FXY+3%DSS and FXY+2%DSS groups, while concentrations of DAI, colon weight, colon weight index, colon weight/colon length, pro-inflammatory cytokines TNF-ɑ, IL-1β and IL-6 were significantly increased, and significant ulcer formation and inflammatory cell infiltration were observed under light microscopy. Compared with the Control group, the percentages of CD4, Th1 and Th17 cells in the mesenteric lymph nodes of FXY+3% DSS and FXY+2% DSS groups were significantly increased, while CD8, Th2 and Treg cells were significantly decreased. Conclusion The combination of Senna and 2% DSS could successfully construct a model of mice with ulcerative colitis with spleen deficiency and dampness evidence, showing typical CD4/CD8, Th1/Th2 and Th17/Treg cell imbalance characteristics.

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• Progress in the application of the zebrafish model in the study of neurodegenerative diseases

  Liu Yanying

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  Abstract:

  【Abstract】 With the process of the aging society, the incidence rate of neurodegenerative diseases is increasing year by year. Zebrafish have many advantages that other model organisms do not have, such as unique growth and development mode, low price and easy reproduction, and highly similar to human genes. In the past decades, zebrafish as a model organism has been widely used in various research fields of medicine and life science. This article reviews the application and progress of zebrafish in the research of several common neurodegenerative diseases in recent years, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, hereditary spastic paraplegia, and other diseases related to the nervous system. This review article analyzes and summarizes the advantages and disadvantages of zebrafish as an ideal model organism. In future research, especially in the mechanism research of neurodegenerative diseases and large-scale screening of therapeutic drugs, zebrafish has considerable application prospects.

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• Research progress on animal model construction and evaluation of different TCM syndromes of gastric ulcer

  Wang Wen, Hou Yujun, Wang Lu, Yan Xiangyun, Li Yanqiu, Sun Luqiang, Chen Shuai, Shi Yinzhou, Zheng Qianhua, Li Ying

  Abstract: (31) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  Gastric ulcer is a common digestive system disease. Traditional Chinese medicine (TCM) has a significant effect in treatment of this disease. However, its treatment mechanism is unclear. Establishing a scientific and objective animal model and model evaluation system is of great significance to promote development of TCM in this field. This article organizes the literature related to treatment of gastric ulcer by TCM in the past 10 years and summarizes methods for establishing and evaluating animal models of TCM syndromes relating to gastric ulcer. The methods were reviewed for liver and stomach disharmony syndrome, spleen and stomach dampness-heat syndrome, blood stasis in stomach syndrome, deficiency cold of spleen and stomach syndrome, stomach Yin deficiency syndrome, and liver depression and spleen deficiency syndrome. The current animal models of gastric ulcer had the following problems: the typing of TCM syndromes was not unified, the methods and syndrome types of the models were limited, the standards of model establishment methods were different, the combination of disease and syndrome of models was not close enough, and the model evaluation system was not standardized. Suggestions for model improvement are proposed to provide a reference for research in this field.

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• Analysis of pathological changes of knee joint and intestinal tissue in cynotonic spondylitis monkeys

  huangyuye, caiyanzhen, caichunmei, zhuhepeng, dinghuangguan, xiaowende, chenjun, luli

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  Abstract:

  Objective: Ankylosing spondylitis (AS) is an immune-mediated chronic disease involving axial joints, peripheral joints and intestines, but the etiology of peripheral knee and intestine has been unknown. This study aimed to study the main pathological changes and mechanisms of knee joint and intestine in cynomolgus monkeys with AS. Methods: Through histomorphological analysis and immunohistochemical experiments, the key characteristics of peripheral knee joint and intestinal tissues of AS were studied and the possible pathogenesis was preliminarily analyzed. Results: The pathological characteristics of peripheral knee joints in AS cynomolgus monkeys mainly showed cartilage erosion on the joint surface, exposed subchondral bone, and jagged joint surface in the early stage. In the late stage, it is mainly manifested as ectopic hyperplasia of cartilage superficial hypertrophy of chondrocytes, and osteophytes are formed through chondroplaginous osteogenesis and fibroogenesis, and cartilage is basically lost. The expression of MMP-3 in cartilage and blood vessels is upregulated, causing cartilage destruction and stimulating angiogenesis. AS cynomolgus monkeys have severe atrophy of small intestinal villi and obvious crypt hyperplasia, and a large number of γδ T cells can be seen in the mucosal intestinal glands of the jejunum and ileum. Conclusion: In this study, the pathological analysis of knee joint and intestine of AS cynomolgus monkey obtained the key characteristics of knee joint and intestinal tissue of this spontaneous model, and proposed a possible pathogenesis. This paper provides new insights into the potential link between autoimmunity in bone tissue and intestinal tissue lesions in AS.

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• Langendorff Cardiac Perfusion Technique (for Myocardial Ischemia Reperfusion) applications and developments

  Linan, Zhang Chen, Sun yanjun, Gao Shengwei, Li Duojing, Wang xinrui, Wang Baohe

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  The Langendorff ex vivo cardiac perfusion model technique is reproducible, easy to administer and has low technical requirements, and is often used to study myocardial ischemia-reperfusion injury diseases. This article reviews the steps of this technique, selection of animals, perfusion patterns, selection of perfusate, indices of detection, ischemic modalities, and selection of ischemia and perfusion times.

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• Study on the antidiarrheal effect of new "Ershen pills", a composition of new sliced nutmeg Koji

  Fan Mengmeng, Li Kai

  Abstract: (23) HTML (0) PDF (0.00 ByteKB) (0)

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  Objective To evaluate the antidiarrheal effect of new ershen pills composed of nutmeg koji instead of bran stewed nutmeg.Method Kunming mice were randomly divided into normal group, model group, Ershen pills Ⅰ (salt psoralen + bran stewed nutmeg), Ershen pills Ⅱ (salt psoralen + nutmeg koji), Ershen pills Ⅲ (salt psoralen + nutmeg raw product), salt psoralen group, and nutmeg koji group. The combined modeling method of "hydrocortisone + senna leaf" was used to establish the diarrhea mouse model with spleen-kidney Yang deficiency. The general signs and pathological changes of each organ were observed. The levels of various organs index, small intestine propulsion rate, gastric residual rate, serum motilin (MTL), gastrin (GAS), adrenal ketone (CORT), thyroid stimulating hormone (TSH), testosterone (T), tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) were detected. 16S rDNA sequencing and information analysis were conducted for fecal microorganisms. Results After modeling, compared with normal group, the weight and activity of mice in model group were reduced, small intestine propulsion rate was significantly increased, gastric residual rate and organ index were significantly decreased, serum GAS, CORT, TSH and T levels were significantly decreased, MTL, TNF-α and IL-β levels were significantly increased, and intestinal flora species diversity was decreased. After administration, the above indexes and symptoms were improved in different degrees in each administration group, and Ershen Pills group Ⅱ was better than Ershen Pills group Ⅰ, Ershen Pills group Ⅲ, salt-psoralea and myristoqu groups. Conclusion The combined use of nutmeg koji and salt psoralen has a remarkable effect on the diarrhea of spleen and kidney Yang deficiency. The fermented nutmeg can reduce its toxic risk and enhance its effect of warming spleen and preventing diarrhea, which laid a foundation for the development of nutmeg koji.

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• Characteristics and application analysis of ovarian cancer animal model

  yi chu, zhan sha, ma xin yi, wu yang jie, bu jun yi, ma min, yan xian xin

  Abstract: (45) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  【Abstract】Objective To study the characteristics and application status of animal models of ovarian cancer and provide guidance for standardized preparation of ovarian cancer models. Methods Using “ovarian cancer” and “animal model” as the main topics in CNKI, Wanfang, VIP, and PubMed databases, the databases were searched for animal experimentation literature on ovarian cancer from establishment of the database to March 1, 2023. A total of 1428 relevant articles were collected. From the experimental animal species, age, experimental modeling methods, detection indicators, and other aspects of the summary, we established a database for systematic analysis. Results A total of 178 studies were obtained after screening. Female BALB/c mice were selected to establish the animal model of ovarian cancer. Most choices were 4 ~ 6 and 6 ~ 8 weeks of age. The most common modeling method was ectopic transplantation, which was mostly subcutaneous injection in the axilla. In terms of modeling methods of ovarian cancer in animals, transplantable models were the most used, and ectopic transplantation was more often employed than orthotopic transplantation. The ovarian cancer cell lines used were mostly human. Most detection indexes were the appearance of tumor tissue, tumor pathology, and immunohistochemistry. Conclusion Animal models of ovarian cancer are widely used in ovarian cancer research, but standard preparation and evaluations are lacking. We analyzed the application status of animal models of ovarian cancer in detail through literature collation and data classification analysis to provide a reference to establish standardized animal models of ovarian cancer. BALB/c mice are the most selected, and human ovarian cancer cell line SKOV3 at 1 × 107 cells/ml is commonly injected into the subcutaneous axillary area for 10 days. A large number of models can be obtained in a short time with a high tumor formation rate and small individual differences, which provide a reference to study ovarian cancer.

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• Model establishment and evaluation of rats with chronic obstructive pulmonary disease complicated with chronic kidney disease

  Fanzhengyuan, Li Ya, LI Suyun, LI Gaofeng, LI Jingmei

  Abstract: (27) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  Objective To establish and evaluate a model of chronic obstructive pulmonary disease (COPD) combined with chronic kidney disease (CKD) in rats. Methods Forty SPF grade SD rats were randomly divided into control, COPD, CKD, and COPD combined with CKD model (COPD+CKD) groups, with 10 rats in each group. The COPD rat model was prepared by cigarette smoke exposure combined with the bacterial drip method, the CKD rat model was established by adenine induction, and the COPD combined with CKD rat model was prepared by both methods. Results After successful modeling, lung function indexes incluidng forced vital capacity (FVC), forced expiratory volume in 0.1s (FEV0.1), and FEV0.1/FVC were significantly reduced in the COPD+CKD group (P < 0.01), and lung histopathology showed emphysematous changes with alveolar wall fracture and fusion as well as inflammatory cell infiltration. Serum Cr, BUN, and 24 h urine protein were significantly increased (P < 0.01). Renal histopathology showed glomerular mesentery proliferation, basement membrane thickening, tubular dilatation, and interstitial fibrosis. The ultrastructure showed that glomerular capillary loops were partially closed, foot processes were fused, renal tubule mitochondria were fused and disintegrated, and lysosome was increased. Serum IL-6, IL-13, IL-1β, and TGF-β1 levels were significantly increased (P < 0.01) and were significantly higher than those in single model groups (P < 0.01). Conclusions Cigarette smoke exposure combined with bacterial infection and 2.5% adenine induction successfully establishes a model of COPD complicated with CKD in rats, and the inflammatory response might play a major role in the process of COPD complicated with CKD.

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• Research progress of functional dyspepsia animal model based on the combination of disease and syndrome

  liuhao, wangxinai, liwenjing, wuyaxuan, wangchenqi, xiaohongling

  Abstract: (27) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  Functional dyspepsia (FD) is a non-organic disease mainly due to regional dysfunction of stomach and duodenum. In traditional Chinese medicine(TCM), it is classified as "epigastric fullness" and "epigastric pain", and divided into the syndrome types of spleen deficiency and qi stagnation, spleen-stomach deficiency-cold(weak), spleen-stomach damp-heat, liver-stomach disharmony, and cold- heat complicated. TCM has a significant effect and high acceptance in the treatment of FD, and the animal model with the combination of disease and syndrome is the basis and prerequisite for relevant research. Therefore, this paper organized and summarized the existing research on animal models of FD combined with disease and syndrome, explored the reasons for the selection of specific modeling methods and evaluation indicators, and proposed the shortcomings of the current research, in order to provide support for the future research on animal models of FD combined with disease and syndrome.

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• Collagen peptide combined with sodium alginate improved intrauterine adhesions in mice by down-regulating the expression of NLRP3 inflammasome

  chengyiyi, zhaoweiwei, song zhenfeng, tongfuwen, liugang, zhanghua, shileilei, guozhikun, wangxianwei, panying, sunyongkun

  Abstract: (41) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  【Abstract】Objective To investigate the repair effect and mechanism of collagen peptides (CP) combined with sodium alginate (SA) on endometrial injury. Methods Forty-eight SPF female C57BL/6N mice were randomly divided into sham group (16 mice), model group (16 mice) and CP SA group (16 mice). In the model group, 95% ethanol was injected into the uterine cavity through the cervix to induce endometrial injury, and the intrauterine adhesion model was established. The sham operation group was injected with 0.9% normal saline into the uterine cavity. The treatment group was injected with the mixture of CP SA after the injection of 95% ethanol into the uterine cavity. After 7 days of modeling, 8 mice in each group were selected to collect samples for each test. HE staining was used to observe the pathological changes of mouse uterine tissue. Modified Masson tri-color staining was used to observe endometrial fibrosis. Western blot was used to detect the protein expression levels of inflammatory factors NLRP3, ASC, Caspase-1, IL-1β and IL-18 in uterine tissues. ELISA was used to detect the expression of IL-1β and IL-18 in serum. The remaining 8 mice in each group were cohoused according to the male-female ratio of 1:2, and the number of pregnant mice in each group was recorded. Pregnant mice were euthanized in the 14th day of pregnancy, and the number of embryos was recorded. Results (1) Compared with the sham operation group, the model group showed thinner endometrial thickness, increased endometrial fibrosis, and inflammatory cell infiltration. In addition, the protein expression levels of inflammatory factors NLRP3, ASC, Caspase-1, IL-1β and IL-18 in uterine tissue and the levels of IL-1β and IL-18 in serum in the model group were significantly lower than those in the sham operation group (P<0.05). (2) Compared with the model group, the treatment group showed that the degree of endometrial injury, endometrial fibrosis and inflammatory cell infiltration were reduced. In addition, the protein expression levels of inflammatory factors NLRP3, ASC, Caspase-1, IL-1β and IL-18 in uterine tissue and the levels of IL-1β and IL-18 in serum in the model group were significantly decreased than those in the sham operation group (P< 0.05). (3) Compared with the sham group, the reproductive ability of the model group decreased (P<0.05). Compared with the model group, the reproductive ability of the treatment group was significantly improved(P<0.05). Conclusions The combined application of CP and SA can effectively improve the pathological changes of uterine tissue, reduce endometrial injury, inflammatory response and fibrosis, and improve the reproductive ability of mice. The mechanism may be related to the down-regulation of NLRP3 inflammasome expression, which provides a reliable experimental basis for the combined application of CP and SA in the treatment of intrauterine adhesion.

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• Research progress of bronchoalveolar lavage in mice

  Wu Zhihao, Yang Luyin, Ren Wei, Zhou Yanan, Wang Hong, LeiYun, Yu Hong, Yang Sijin

  Abstract: (63) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  Bronchoalveolar lavage is an important technique for studying respiratory diseases and has been widely used in disease research. Currently, the operation procedure of bronchoalveolar lavage in clinical patients has been gradually standardized, while mice, as one of the important model animals for studying lung diseases, still need a standard collection and testing procedure for bronchoalveolar lavage fluid for mice. An unstandardized procedure can hinder the promotion and application of this technique in research, and also affect the accuracy and reliability of experimental results. This paper presents a systematic summary of bronchoalveolar lavage methods for mice in domestic and international studies, with the aim of providing reference and guidance for researchers to apply and establish a standardized lavage procedure in the future.

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• Advances in Animal model for studying albumin-related drugs

  Ziyin, Ning Li, Tang Chengcheng, Zhou Xiaoqing

  Abstract: (53) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  The main challenges of therapeutic peptides or proteins is their short plasma half-life. The drugs combining these peptides or proteins were defined as albumin-related drugs. Such combination can effectively prolong the plasma half-life. Animal model is an important and indispensable tool for studying drug pharmacokinetics. This review summarizes two main animal models; rodents (wild-type mice, gene-modified mouse models, rat models) and non-rodents (monkeys), and their development and application in albumin-related drugs. This review can provide a reference for further studies on albumin-related drugs.

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• Research progress on the establishment of mouse atherosclerosis model by different intervention factors

  baixufeng, cao qingyu, 胡, wang shuwen, liu yali

  Abstract: (59) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  Atherosclerosis (AS) is a potential risk factor for common cardiovascular and cerebrovascular diseases. Prevention and treatment of AS and research and development of anti-AS drugs have been a focus in the field of medicine. Selection of the ideal AS animal model is important to study prevention and control measures of AS and to research and develop traditional Chinese medicine for AS. The ideal animal model of AS should have similar pathogenesis to human AS, consistent pathological and biochemical reactions, high repeatability, simple operation, and easy adoption. Mice have the characteristics of strong reproduction, high heritability, good plasticity, and fast modeling of AS, and they have become ideal animals for AS research. In this article, the replication methods of the mouse AS model established by various intervention factors were compared and analyzed to provide a reference and ideas for prevention and treatment of AS and research and development of traditional Chinese medicine for AS.

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• 123456

  dong

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• Application and development of germ-free animals for the gut microbiome research

  Hu Yaqian, Wang Shanshan, Zhang Tong, Yuan Jiali, 胡

  Abstract: (65) HTML (0) PDF (0.00 ByteKB) (0)

  Abstract:

  In recent years, with the introduction of the concept of metagenomics, human metagenomics has also become a new approach to reveal the development and health of humankind. As the largest microflora in the human body, the gut microbiome has been found to play an important role in the normal physiological functions of the human body and the occurrence and development of diseases. The variety and quantity of gut microbiome are abundant. In the study of gut microbiome, the application of germ-free animals makes the experiment more accurate and convenient. It is an ideal basic animal model. Not only that, models developed on this basis are also of great significance to this type of research. This review summarizes the understanding of germ-free animals, the application of germ-free animals in experimental research and the prospects of germ-free animal models, to review the application and development of germ-free animals in the gut microbiome.

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Volume 31,2023 Issue 7

研究进展

• Research progress in animal models and mechanism of depression

  HAN Yuan-yuan, DAI Jie-jie

  2016,24(3):321-326, DOI: 10.3969/j.issn.1005-4847.2016.03.020

  Abstract: (6927) HTML (0) PDF (774.13 KKB)(6191)

  Abstract:

  The incidence of depressive illness is high worldwide, and the inadequacy of currently available drug treatments contributes to the significant health burden associated with depression. Animal models of depression used as the main methods to study the pathogenesis mechanism and select effective drugs receive increasing concerns. Current popular models of depression creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology. In this context, this study aims to review the animal models of depression and pathogenesis related with face validity, construct validity, and predictive validity of these models. These models include stress-induced models, injury-induced models, drug-induced models and transgenic models which all mimic the depression symptoms of human to some degree and are of great value for developing new antidepressant drugs and studying the pathogenesis of this disease.

研究报告

• Differential analysis of the bacterial community composition in mouse feces and intestinal contents

  WU Ya-qi, ZHONG Gen-shen, WU Min-na

  2015,23(3):249-255, DOI: 10.3969/j.issn.1005-4847.2015.03.006

  Abstract: (7378) HTML (0) PDF (1.18 MKB)(3935)

  Abstract:

  Objective To explore the objectivity and scientificity of fecal sampling, and to provide reference for investigating the relationship between intestinal microbes and diseases. Methods Terminal restriction fragment length polymorphism, degeneration gradient gel electrophoresis and real time fluorescent quantitative PCR techniques were applied to differentially analyze the bacterial community composition and abundance of intestinal contents and feces taken from different sites of BALB/c mouse intestine. Results The predominant T-RFLP fragments (T-RFs) in feces in the rectum and colon were 244 bp, 255 bp and 449 bp, however, those in feces of the small intestine including duodenum, jejunum and ileum were 60 bp, 73 bp, 261 bp, 268 bp and 272 bp, and with a larger variation of the bacterial community composition in various parts of the small intestine. The bacterial abundance in the contents of duodenum and jejunum were 6.9 log (copies)/g and 8.3 log (copies)/g, fewer than in the other parts of the intestine, while the bacterial abundance in the feces was as high as 11.8 log (copies)/g, being about 2 times higher than that in the duodenum and jejunum (P<0.05), and similar to that in the ileum and colon content (P>0.05). Conclusions The inter-mouse variations of bacterial community composition in the large intestine contents are small. The bacterial composition and abundance are similar suggest that studies on the relationship between large intestine especially colorectal microbiota and diseases may be conducted via fecal sampling.

• Comparison on the preparation of rat models of pneumonia by different infection route

  DING Jun-ying, GAO Xiang, HONG Yan-ying, GUI Hong, WEI Zhi-you, LU You-ran, AN Shi-dong, CUI Xu-ran, GUO Yu-hong, LIU Qing-quan

  2017,25(6):600-604, DOI: 10.3969/j.issn.1005-4847.2017.06.003

  Abstract: (3512) HTML (0) PDF (4.05 MKB)(3776)

  Abstract:

  Objective To explore the preparation of a rat model of pneumonia model induced by Pseudomonas aeruginosa(PA) using different methods,and to lay the foundation for further studies.Methods 48 SD rats were randomly divided into 4 groups:the control group (A),the intratracheal injection group (B),the trachea cannulation group (C) and the intranasal inoculation group (D).After intervention with different treatment modalities,the body weight,temperature,white blood cell count and lung pathological changes in the rats of all groups were detected at 5,10,15 days.Results 1.The behavior,body weight,temperature,leukocytes and pathological inflammatory changes of the lung in rats of the model groups were significantly different from that of control group.2.Pseudomonas aeruginosa was detected in rats of all the model groups,but the control group was negative.Conclusions Rat model of Pseudomonas aeruginosa infected pneumonia can be successfully established by intranasal inoculation.This method can avoid the inflammatory interference from operation,and is simple and suitable for popularization.

• Comparison and improvement of three methods for primary culture of rat embryonic cortical neurons

  LIAO Hui-dan, LONG Ling-ling, YAN Jie

  2015,23(4):410-414, DOI: 10.3969/j.issn.1005-4847.2015.04.015

  Abstract: (3539) HTML (0) PDF (1.35 MKB)(3484)

  Abstract:

  Objective To compare three methods for culture of fetal cortical neurons of SD rats and find out the suitable culture conditions of fetal cortical neurons in vitro. Methods The cortex of 16-18-day embryonic rat was used for culture in this study. Mechanical dissociation, trypsin digestion and papain digestion were applied respectively to the neuron culture. The morphological characteristics of neuronal cells at different time points were observed and neuron purity was identified by immunofluorescence staining assay. Results High purity of the fetal rat cortical neurons was successfully achieved by all the three culture methods, and each had distinct morphological characteristics at different time points. The purity of neurons was 96.28%, 95.63% and 97.34%, respectively, with no significant differences among the three groups (P>0.05).Conclusions The three culture methods are improved in our study. Stable neurons with high purity can be obtained by all the three methods respectively, and each of these methods has distinct characteristics.

研究进展

• Application of Chinese Bama minipigs in medical research：a literature review

  PANG Lin-lin, ZHANG Hui-yong, YANG Guan-lin

  2014,22(1):94-98, DOI: 10.3969/j.issn.1005-4847.2014.01.020

  Abstract: (9763) HTML (0) PDF (711.74 KKB)(3054)

  Abstract:

  As one of the major domestic minipig strains, Guangxi Bama minipigs have the following characteristics: genetic stability, fecund species, lighter weight, large area of body surface covered with white hairs, many tissues and organs and biochemical indicators similar to those of humans and so on. All these characteristics make them being widely applied in medical research. Because of the similar anatomy and physiology in cardiovascular system, Bama minipigs have been used in the research of cardiovascular system. In our country, Bama minipigs are used for establishing models of cardiovascular diseases such as myocardial ischemia, patent foramen ovale and so on. Pigs are omnivore-animals and similar to human beings in lipid metabolism, so they can be used in the study of endocrine diseases. Bama minipigs have been used in modeling, genetic susceptibility and complication prevention of diabetes. Bama mini-pigs' digestive system is similar to that of humans, so they can be used as a model of digestive system diseases including chronic pancreatitis, rupture of colon and bilioenteric anastomosis. The aspect that large area of their body surface is covered with white hairs except their head and tail makes them ideal model of skin wound and healing of burns. Bama minipigs can be used for stomatological research for their similarity to human beings in the structure of the teeth and large crack. Bama minipigs have been applied for the research of pulp necrosis and the way of maxillary expansion. They are similar to human beings in anatomy, physiology and pathology, which makes them an appropriate provider for zenotransplantation. In the research of traditional Chinese medicine, Bama minipigs has been used as liver, spleen and femoral arteriovenous fistula hemorrhagic model to study curative effect and mechanism of traditional Chinese preparation.

• Advances in mouse models of colorectal cancer

  MIAO Jinxin, SONG Shaohe, LI Xiumin

  2020,28(2):0-0, DOI: 10. 3969 / j.issn.1005-4847. 2020. 02. 018

  Abstract: (2113) HTML (0) PDF (754.50 KKB)(3038)

  Abstract:

  Colorectal cancer is one of the most common malignant tumors worldwide, and the morbidity and mortality rate is increasing year by year with patients tending to be younger. The colorectal cancer mouse model increases our understanding of human colorectal cancer characteristics and cancer prevention and treatment. Murine models of colorectal cancer can be divided into spontaneous, induced, transplanted tumor, and transgenic models. However, none recapitulate all the characteristics of human colorectal cancer. The use of a specific mouse colorectal cancer model to address specific colorectal cancer research issues is critical. This paper has examined research literature both domestic and foreign to provide a review of the research progress of different mouse models of colorectal carcinoma over the past 20 years. The aim is to establish a suitable mouse model for the study of colorectal cancer.

• Research progress in establishment and application of mouse models of leukemia

  MA Chang, GUO Jianmin, XIE Songqiang, YANG Wei

  2019,27(2):266-270, DOI: 10. 3969 / j.issn.1005-4847. 2019. 02. 022

  Abstract: (2297) HTML (0) PDF (184.93 KKB)(2929)

  Abstract:

  Leukemia is often referred to as a “blood cancer”. The basic characteristic of the disease is thatleukemic cells become malignant and cause unrestricted proliferation in the bone marrow and other hematopoietic tissues.Then, these cells infiltrate all tissues and organs of the body causing various symptoms, and make patients prone to seriousinfections and life-threatening complications such as sepsis, hemorrhage, intestinal failure or hyperuricemia. Therefore,research on the treatment of leukemia using laboratory animal models is of great significance. For the study of leukemia,mice are similar to humans in terms of biology, genetics, and hematopoietic systems, and are, therefore, ideal models forleukemia research. This article reviews the mouse models of leukemia used commonly in studies both in China and abroad in the past 5 years.

研究报告

• Exploration of the establishment of a rat model of chronic diabetic skin ulcer simulating the traditional Chinese syndrome

  LI Yuan, ZHAO Guang-ming, DONG Jian-xun, LU Guang-lin, ZHANG Xu-hui, WANG Le-ping

  2014,22(1):63-66, DOI: 10.3969/j.issn.1005-4847.2014.01.012

  Abstract: (5894) HTML (0) PDF (718.78 KKB)(2842)

  Abstract:

  Objective To observe the effects of different modeling methods on the wound morphology and healing time of chronic skin ulcers in diabetic rats. Methods SD rats (n=50) were randomly divided into five groups, 10 rats in each group: skin defect group (group QS: dermal deficiency), diabetes group (group DM: STZ injection+skin excision), diabetes plus Staphylococcus aureus group (group DMJJ: STZ injection+skin excision+bacterial infection), diabetes plus hydrocortisone group (group DMJS: STZ injection+skin excision+hydrocortisone intervention) and diabetes plus hydrocortisone and implantation of foreign body group (DMYW group: STZ injection+skin excision+hydrocortisone intervention + foreign body embedded). The rats were measured for body weight and wound healing every day, and blood glucose after stable diabetes once a week. The rats were sacrificed 12 days later and the skin lesions were examined by histopathology.Results The healing rate of the DMYW group was significantly slower than that in the other groups (P<0.01). At 12 days after modeling, the healing rate of the DMYW group was significantly lower than that of the remaining groups (P<0.01), while the healing rates were not significantly different among the remaining groups.Conclusions The modeling method of DMYW group can show skin wounds similar to the clinical characteristics of "Yin syndrome", and the addition of foreign body implantation significantly prolongs the rat skin healing time.

• Establishment of a mouse model of aorta dissection induced by β-aminopropionitrile drinking combined with angiotensin II infusion

  LIU Yu-ting, GAO Yan-xiang, WANG Shan-shan, REN Wei, SUN Wei-liang, YU Chang-an, ZHENG Jin-gang

  2017,25(4):399-403, DOI: 10.3969/j.issn.1005-4847.2017.04.010

  Abstract: (6422) HTML (0) PDF (3.32 MKB)(2826)

  Abstract:

  Objective To establish a mouse model of aorta dissection (AD) by β-aminopropionitrile (BAPN) in drinking water + subcutaneously pumped angiotensin Ⅱ (Ang Ⅱ) infusion. Methods Forty 3-week-old C57B1/6J male mice were randomly divided into two groups. All animals received 0.1 g/kg/d BAPN in drinking water for 4 weeks. Then the BAPN drinking + saline infusion group and BAPN drinking + Ang Ⅱ infusion group received continuous saline or Ang Ⅱ (1,000 ng/kg/min) infusion, respectively, via subcutaneous osmotic minipump for 72 hour. The mice were restricted in a noninvasive computerized tail-cuff system and their arterial systolic blood pressure and heart rate were monitored. Autopsy was performed if a mouse died during the experiment. At the end of the experiment, mice were sacrificed by injection with an overdose of sodium pentobarbital and the aortas were harvested. The formation of aortic false lumen was observed by pathology using hematoxylin-eosin staining. Results The overall incidence of AD in the BAPN drinking administration +Ang Ⅱ infusion group was 95%, whereas the incidence of AD in the BAPN drinking administration +saline infusion group was only 5%. The mortality from dissecting aneurysm rupture was 24% in the BAPN drinking administration +Ang Ⅱ infusion group during the experiment. Pathological examination of the aortic cross-sections clearly showed the formation of blood-filled false lumens induced by Ang Ⅱ. Conclusions A mouse model with high incidence of aortic dissection is successfully established.

研究进展

• Research progress of animal models of renal fibrosis and their characteristics

  MA Yuanyuan, LIU Chenghai, TAO Yanyan

  2018,26(3):398-403, DOI: 10.3969/j. issn. 1005 -4847. 2018. 03. 020

  Abstract: (1930) HTML (0) PDF (813.95 KKB)(2823)

  Abstract:

  Renal fibrosis is a common pathological pathway of chronic kidney diseases that leads to end?stage renal failure. The pathological changes include glomerulosclerosis and renal interstitial fibrosis. Ideal animal models for the study of pathologic mechanisms and drug development of chronic kidney disease are of great significance. At present, the method of establishment of animal models include drug or toxin induction, surgical models and gene knockout, etc. Different animal models have various characteristics of renal function and pathology, but can not completely simulate human chronic kidney disease, suggesting the complexity of chronic kidney diseases. So the preparation and research of the animal models is important for understanding the pathological mechanisms, prevention and treatment of renal fibrosis.

• The significance of a non⁃invasive measurement of lung function in mice

  LI Shumin, ZHANG Min, WANG Peng, HONG Fan, WANG Chen, ZHANG Yue, GENG Zhenyang, YANG Xinyu, HE Xiaoxiao, SUN Ying, YANG Fang

  2018,26(5):548-553, DOI: 10.3969/j. issn. 1005 - 4847. 2018. 05. 002

  Abstract: (2451) HTML (0) PDF (816.28 KKB)(2674)

  Abstract:

  Objective To provide a reference for studies of monitoring lung function in mice, this study was aimed to test the indexes of a non?invasive measurement of lung function in mice. Methods Lung function indexes of 460 C57BL/6 mice were detected by whole?body plethysmography. The results were analyzed, and the range of reference values was determined by the percentile method. Results Normal ranges for the following measures were found: inspiration time was 64. 7 (55. 30 -82. 60) ms, expiration time was 83. 4 (71. 70 -109. 20) ms, Rpef was 0. 21 (0. 16 -0. 28) ms, end?inspiratory pause was 2. 19 (1. 96 -3. 76) ms, end?expiratory pause was 1. 67 (0. 12 -9. 15) ms, tidal volume was 0. 44 (0. 25 -0. 58) mL, enhanced pause was 1. 29 (0. 91 -2. 00) ms, pause was 1. 18 (1. 00 -1. 64) ms, expiratory flow?50 was 0. 64 (0. 30 -0. 98) mL/ s, relaxation time was 39. 0 (32. 40 -51. 50) ms, peak inspiratory flow was 9. 74 (5. 33 -12. 83) mL/ s, peak expiratory flow was 9. 86 (5. 12 -13. 47) mL/ s, inspiratory frequency was 412 (331 - 474) BPM, and minute volume was 174. 4 (86. 69 -235. 04) mL. Conclusions The normal reference ranges from non?invasive lung monitoring in C57BL/6 mice can be used as a reference for basic research on respiratory diseases.

研究报告

• Establishment of a method for culture in vitro of peripheral blood monocytes from rhesus macaque

  SANG Ming, DAI Ming, ZHOU Li, LIU Jin-biao, GUO Ming, MA Tong-cui, XIAO Qian-hao, HO Wen-zhe

  2015,23(1):18-24, DOI: 10.3969/j.issn.1005-4847.2015.01.004

  Abstract: (8324) HTML (0) PDF (985.49 KKB)(2641)

  Abstract:

  Objectives To establish a simple, inexpensive and efficient technique for in vitro culture of monocyte-derived macrophages (MDM) from rhesus macaques of Chinese origin. Methods Peripheral blood of healthy rhesus macaques (Macaca mulatta) were obtained in heparinized vacutainer collection tubes. Peripheral blood mononuclear cells (PBMCs) were isolated from blood by Ficoll gradient centrifugation. Serum was isolated from peripheral blood of the autologous animals. PBMCs were plated in 48-well-plate (3×10⁶ cells/well) or 96-well-plate (0.8×10⁶ cells/well) for 24 h. After removal of non-adherent cells from the culture, monocytes were cultured in RPMI 1640 supplemented with different proportions (2%, 4%, 8%, 10%) of autologous serum or fetal calf serum (FCS) for 7 days. To examine the biological function of MDM, lipopolysaccharide (LPS) was added to MDM culture to determine inflammatory cytokine production. Also, MDM cultures were tested for the susceptibility to simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) infections. Results The cell cultures with RPMI1640 containing 2% autologous serum yielded the best results with regard to macrophage morphology, the response to LPS stimulation and susceptibility to SIV or SHIV infection. The purity of adherent macrophages under condition of 2% autologous serum culture was higher than 96%. Conclusions RPMI 1640 with 2% autologous serum is suitable for culture in vitro of peripheral blood monocytes from rhesus macaques. This technique is simple, inexpensive, no need for growth factor and highly effective to obtain adherent and well differentiated macaque monocytes. Therefore, this method provides an important tool for culture of macaque AIDS viruses and for related immunological research.

研究进展

• Research progress on establishment of animal models of ovarian cancer

  LI Dongdong, WANG Li, ZHONG Jie, LING Chenqi, LIANG Yanping

  2018,26(2):259-264, DOI: 10.3969/j. issn. 1005 -4847. 2018. 02. 021

  Abstract: (2008) HTML (0) PDF (793.39 KKB)(2492)

  Abstract:

  Ovarian cancer is the fifth leading cause of cancer?related death in women. 75% of ovarian cancer patients were detected at an advanced stage. At present, the disease lacks effective early screening method and the clinical therapy effect is poor, which has become a serious threat to women’s health. The use of animal models of ovarian cancer is an important mean to elucidate the pathogenesis of the disease, and to screen effective diagnosis and treatment. The disease models are mainly divided into four types: spontaneous, induced, transplanted and gene intervention type. Mice, rats, hens, Mirotus Fortis and Mongolian gerbil are mainly selected to prepare animal models of ovarian cancer. Based on recent literature reports, we reviewed the preparation method of animal models of ovarian cancer and introduced the evaluation standards and main characteristics of these animal models.

研究报告

• Oxidative stress in the rat models of Parkinson's disease dyskinesia with Yin deficiency stirring wind pattern, and the interventional effect of compound formula Rehmannia on the disease condition

  TENG Long, HONG Fang, HE Jian-cheng

  2015,23(1):25-29, DOI: 10.3969/j.issn.1005-4847.2015.01.005

  Abstract: (6257) HTML (0) PDF (756.47 KKB)(2463)

  Abstract:

  Objective To explore the oxidative stress in Parkinson's disease dyskinesia with Yin deficiency stirring wind pattern, and the interventional effect of compound formula rehmannia on the disease condition. Methods One hundred and twenty healthy male SD rats (body weight 180-200 g) were randomly divided into four groups: the control group, sham-operated group, model group, and Rehm group. The rat model with Parkinson's disease (PD) was established by injection of 6-hydroxyl dopamine to destroy the substantia nigra using the brain stereotaxic apparatus. Dyskinesia was induced in the PD rats by injection of levodopa into the brain. The dyskinesia PD model rats received intraperitoneal injection of levodopamine 50 mg/kg and benserazide 12.5 mg/kg for 2 weeks to induce Yin deficiency stirring wind pattern. The rats of Rehm group were given gastric gavage of compound formula rehmannia 2 mL/kg once a day for 4 weeks or 6 weeks. At the end of experiment (4 weeks and 6 weeks), neurobehavioral examination was performed, and the contents of SOD, MDA, GSH, and GSH-Px in the striatum tissue were assessed by colorimetry. Results In the LID group, the contents of SOD, GSH, GSH-Px in the striatum tissue were significantly lower than those in the normal control group and sham-operated group, and the malondialdehyde (MDA) content showed an increasing trend. In the compound rehmannia prescription group, the concentrations of SOD, GSH, GSH-Px in the striatum tissue showed an increasing trend, even more obvious along with the time course, and the malondialdehyde (MDA) content showed an decreasing trend, also even more obvious along with the time course. Conclusions The compound rehmannia prescription can improve the oxidative stress in rat models of Parkinson's disease dyskinesia with Yin deficiency stirring wind pattern. The interventional effect of compound rehmannia prescription may be mediated by scavenging free radicals and reducing the damage to the cells, thus, to alleviate the symptoms of Parkinson's disease dyskinesia.

• Determination and analysis of blood biochemical parameters of wild and breeding rhesus macaques in Anhui Province

  XU Yu-rui, LI Jin-hua, SUN Bing-hua, XIA Dong-po, ZHU Yong, WANG Xi

  2014,22(1):87-90, DOI: 10.3969/j.issn.1005-4847.2014.01.018

  Abstract: (6845) HTML (0) PDF (701.51 KKB)(2453)

  Abstract:

  Objective To determine the blood biochemical parameters of wild and cage reared rhesus macaques in Anhui Province, and compare the differences between the two kinds of macaques and B virus (BV) positive and negative infection. Methods Fourteen blood biochemical indexes of Anhui rhesus macaques were measured with an automatic blood biochemical analyzer. The differences of biochemical parameters between wild and breeding, and BV positive and negative infection were analyzed. Results The blood biochemical indexes of males were higher than those of females. ALP, TG and GGT showed significant difference between males and females of wild macaques. ALP, ALB, Ca, TG, Cr and GGT showed significant difference between males and females of breeding macaques. The biochemical indexes of BV positive infected monkeys were higher than that of BV negative infected monkeys. Conclusion The blood biochemical parameters are different between wild and breeding macaques, males and females, and BV positive and negative infected monkeys.

• Establishment of a mouse model of H7N9 avian influenza A virus infection

  ZHU Hua, XU Li-li, BAO Lin-lin, DENG Wei, CHEN Ting, LU Qi, LI Feng-di, YUAN Jing, XU Yan-feng, HUANG-Lan, LI Yan-hong, LIU Jiang-ning, YAO Yan-feng, YU- Pin, YONG Wei-dong, WEI Qiang, ZHANG Lian-feng, QIN Chuan

  2014,22(1):18-21, DOI: 10.3969/j.issn.1005-4847.2014.01.004

  Abstract: (9190) HTML (0) PDF (739.37 KKB)(2439)

  Abstract:

  Objective The aim of this study was to establish a mouse model of H7N9 avian influenza A virus infection. Methods Seventy SPF healthy female BALB/c mice were used in this study. A/Anhui/1/2013 (H7N9) avian influenza virus was administered by intranasal instillation to BALB/c mice, inoculated in a dose of 50 μL 1×10⁸, 1×10⁷ or 1×10⁶ TCID₅₀, respectively, 10 mice in each group. Other 30 mice were used for virus titration and pathological examination. Ten mice were given saline as control group. The changes of body weight, clinical signs and death of the mice were observed every 24 h from 1 to 14 d. Blood and several organ samples were taken for pathological examination, and avian influenza A (H7N9) virus was detected with virus titration and immunohistochemistery (IHC). Results The mice developed typical clinical signs including body weight loss, ruffled fur and humped back. The peak of virus shedding from respiratory tract was observed on 2 days post inoculation (d.p.i.), and histopathological examination observed interstitial pneumonia. The virus was also detected in the brain, liver, spleen, kidney and intestine from inoculated mice. The inoculation of H7N9 virus elicited seroconversion titers up to 160. There was reduction of lymphocytes and increase of neutrophils in the blood. Conclusions The mouse model of H7N9 avian influenza virus infection established in this study show similar signs of human avian influenza. Therefore, it provides a useful working basis for research of the pathogenesis, drug development, and vaccine evaluation of this disease.

研究进展

• Review of the process of modeling acute kidney injury

  YANG Ting, LIN Zhijian, JIANG Zhuoxi, CHU Mengzhen, ZHANG Bing, ZOU Lina

  2020,28(1):123-128, DOI: 10. 3969 / j.issn.1005-4847. 2020. 01. 018

  Abstract: (1490) HTML (0) PDF (807.00 KKB)(2422)

  Abstract:

  Establishing a stable and reliable acute kidney injury model is an important means of researching acute kidney disease. Acute kidney injury models have various modeling method, different application scopes and diverse modeling standards. Acute kidney injury models were classified by reviewing the recent related literature and materials to analyze modeling method, pathological mechanisms, applications, modeling characteristics and other aspects. This work was conducted to provide promising references and considerable guidance for research and practice in treating acute kidney injuries.

• Research progress of animal models of myocardial injury induced by isoproterenol

  LIANG Juan, LIU Yue, YIN Xinhua

  2019,27(1):110-114, DOI: 10. 3969 / j.issn.1005-4847. 2019. 01. 018

  Abstract: (1781) HTML (0) PDF (759.78 KKB)(2382)

  Abstract:

  Cardiovascular disease (CVD) is a leading cause of human death worldwide, but its pathogenesis and prevention still need further research. Isoproterenol (ISO) is a β-adrenergic receptor agonist that acts directly or indirectly on the myocardium through inflammatory responses, oxidative stress, endoplasmic reticulum stress, autophagy, and apoptosis, which can cause mild myocardial injury, myocardial infarction, cardiac hypertrophy, and even heart failure. This review mainly focuses on the research on animal models of myocardial injury caused by ISO and attempts to describe its morphological and functional characteristics, as well as its pathogenesis.

• Measurement of Alu gene expression by RT-PCR in the evaluation of models of gastric cancer metastasis

  WU Pengpeng, LIU Sensen, ZHANG Caiqin, ZHAO Yong, BAI Bing, WANG Jie, SHI Changhong

  2021,29(4):440-447, DOI: 10. 3969 / j.issn.1005-4847. 2021. 04. 003

  Abstract: (1460) HTML (0) PDF (6.63 MKB)(2281)

  Abstract:

  Objective We aimed to characterize the relationship between the expression of the Alu gene in a model of human gastric cancer metastasis and the degree of gastric cancer metastasis in tissues and organs and establish a molecular biological method for the early evaluation of gastric cancer metastasis. Methods Alu gene expression plasmids were constructed from the genomic DNA of human gastric cancer cell lines SGC- 7901, MKN45 and the normal gastric mucosal cell line GES1. Alu gene expression in various concentration of gastric cancer cells SGC-7901, which was widely mentioned as human gastric metastasis cell line, was measured by real-time PCR. The relationship between different Alu expression of various concentration was measured by cycle threshold (Ct) value to modelling the standard curve. A human gastric cancer cell xenograft metastasis model was established by the subcutaneous inoculation of SGC-7901 and MKN45 cells into nude mice. The expression of Alu in the resulting tumors in the mice (in the liver, spleen, lung, kidney, and subcutaneous tissues) was then measured by real-time PCR, and a curve for the relationship between the expression of Alu and the degree of tumor metastasis in each tissue was constructed. Subsequently, fresh tumor samples from patients with gastric cancer were subcutaneously inoculated into nude mice to construct a xenograft model, and the relationships between Alu expression in the tissues of the mice and the degree of tumor metastasis in the organs of nude mice was similarly evaluated. Results The number of SGC-7901 cells negatively correlated with the cycle threshold (Ct) value for the Alu gene (R² = 0. 9239). In the xenograft metastasis model, the expression of the Alu gene was higher in subcutaneous tumors than that in lung and liver metastases, and the expression of the Alu gene in lung and liver metastases was higer than normal nude mice. This was consistent with the result of histopathological examination. In the gastric cancer patient xenograft model, if there was no visible metastasis in the organs of nude mice, the expression of Alu gene (Ct 17. 86) was significantly higher(P< 0. 05)than that of normal nude mice (Ct 22. 18), and if there were metastatic lesions that were visible through the naked eye, the expression of Alu (Ct 14. 29) was very significantly higher than that of normal nude mice (P< 0. 01). Conclusions In a model of human gastric cancer metastasis, the expression of the Alu gene positively correlates with the degree of metastasis, namely the higher expression of Alu, the more metastatic tumor cells were present and the more obvious the metastatic foci were in each tissue.

• Establishment of a BALB / c mouse model of influenza A virus-induced inflammation

  SUN Haiwei, SHI Xinjin, CHEN Yanyan, ZHONG Qiuping, ZHANG Meng, LYU Lu, WANG Jun, CHEN Hongjun

  2019,27(5):571-576, DOI: 10. 3969 / j.issn.1005-4847. 2019. 05. 004

  Abstract: (1842) HTML (0) PDF (845.27 KKB)(2257)

  Abstract:

  Objective The aim of this study was to establish an influenza A virus-induced inflammation model inmice to analyze the pathogenicity of influenza A virus. Methods Forty-four 5-week old SPF healthy female BALB/ c micewere used in this study. A/ swine/ Jiangsu/ C1/08 (H9N2) (H9C1), A/ swine/ Shandong/731/2009 (SD731) and A/Puerto Rico/8/34 ( H1N1) ( PR8) influenza viruses were administered by intranasal instillation to BALB/ c mice,inoculated in a dose of 50 μL 1 × 10⁶ TCID₅₀, respectively, 11 mice in each group. The changes of body weight, clinicalsigns and death of the mice were observed every 24 hours from 1 to 14 dpi (days post inoculation). Blood and lung sampleswere taken for virus titer and inflammation detection. Results Compared with the PBS control group, SD731 and PR8virus infected mice showed a strong inflammation, and the mortality rate of SD731 virus infected BALB/ c mice was 80%and that of the PR8 virus infection was 100%. H9C1 virus infection caused a mild inflammatory response compared toSD731 and PR8 virus infection, and no significant weight loss and no death from 1 to 14 dpi. Conclusions In this study,the successfully established mouse model of influenza A virus-infected inflammation provides a strategy for the study of thepathogenesis of influenza virus, and a useful working basis for research of the pathogenesis, drug development, and vaccine evaluation of this disease.