Abstract:Objective To establish transgenic mouse lineages that can stably express the tandem-dimer tomato (tdTomato) gene and to observe the level of fluorescence expression in tissue sections and stem cells after co-culturing. Methods The gateway clone technique and DNA microinjection were used to construct fertilized ova containing the tdTomato expression vector, which were then transferred to pseudopregnant mice for natural delivery. tdTomato-positive mice were identified and picked using a two-way verification method for breeding and establishment. Neural stem cells from tdTomato-positive mice were co-cultured with bone marrow mesenchymal stem cells and primary neural stem cells from eGFP (green fluorescence protein) mice. Results The tdTomato transgenic mice were successfully constructed, and their lines were established. The biochemical indexes and growth characteristics of the tdTomato transgenic mice did not significantly differ from those of the wild-type mice. Red fluorescence was observed in the tissue sections and brain-derived neural stem cells under fluorescence microscopy. Significant fluorescence was observed at the injection site in the tracer experiments, and two-color fluorescence was stably expressed in the co-culture experiments. Conclusions Stable red fluorescence occurrs in the tissues and cells of the tdTomato transgenic mice, which can be applied to research the direction of differentiation after stem cell co-culturing.

Abstract:Objective To analyze the genetic differences between closed colony and wild population of Mugilogobius chulae, and to establish a genetic quality evaluation method of closed colony M. chulae. Methods Twenty microsatellite markers were selected to detect heterozygosity, genetic differentiation, and the relationship between sample size and the genetic parameters of closed colony and wild population of M. chulae. Results The unbiased expected heterozygosity (He) of closed colony and wild population of M. chulae were 0. 6927 and 0. 7162, respectively. Analysis of genetic differentiation showed little difference between closed colony and wild population. Analysis of the relationship between sample size and genetic parameters showed that the mean number of alleles tended to be stable at a sample size of 30. Conclusions Heterozygosity in the range of 0. 5 – 0. 7 can distinguish closed colony strains of M. chulae from wild population, and would be suitable for determining the genetic quality of closed colony M. chulae.

Abstract:Objective To investigate the gut microbiota changes in quails with hyperuricemia and provide a reference for the pathological mechanism of hyperuricemia. Methods Difalk quails were randomly divided into the normal and model groups and fed a normal diet or high-purine diet, respectively. DNA fingerprinting of the intestinal flora in the cecal contents of quails was performed using the PCR-DGGE method and digitized to analyze the gut microbiota structure via clustering analysis. Logistic regression was used to discern the different bands, and the genes of the different bands were cloned and identified. The cecal tissue was observed via hematoxylin and eosin staining. Results The gut microbiota structure of the model group quails differed from that of the normal group quails on day 28 of the experiment. The DGGE fingerprint contained 12 bands, belonging to Bacteroidetes, Firmicutes, and Proteobacteria. Inflammatory changes occurred in the cecum. Conclusions The gut microbiota structure is altered in quails with high-purine diet-induced hyperuricemia.

Abstract:Objective To validate and compare the functions of calcium supplementation and intestinal peristalsis promotion between two brands of dairy products using zebrafish models. Methods Zebrafish embryos at 3 days post fertilization (dpf) were selected and exposed to UHT(ultra heat treated) milk at 0 (blank control), 2. 5, 5. 0, and 10. 0 mg / mL for 96 h. After treatment, zebrafish were stained with calcein and observed under a stereofluorescent microscope to measure the fluorescence intensity of vertebrae. Zebrafish were also fed with Nile red at 5 dpf for 16 h, followed by a 24 h exposure to the same concentrations of yogurt and lactobacillus beverage. Intestinal tract fluorescence was measured to assess the ability of intestinal peristalsis promotion. Results UHT milk, yogurt, and lactobacillus beverage all increased blank control, 2 of the 6 types of UHT milk increased vertebrate fluorescent intensity; and 8 types of yogurt and lactobacillus beverage significantly elevated intestinal motility, although yogurt was better than the lactobacillus beverage. Conclusions The maximum tolerable concentration (MTC) of UHT milk, yogurt, and lactobacillus beverage is 10. 0 mg / mL in zebrafish. These dairy products have the same functions in zebrafish as in humans in term of calcium supplementation and intestinal peristalsis effect.

Abstract:Objective To isolate and identify the pathogen responsible for causing hemorrhage in Mugilogobius chulae, and to investigate its route of transmission, providing a technical basis for microbial quality control in M. chulae. Methods The pathogen was isolated from the liver of diseased M. chulae. The morphological, biochemical, and molecular characteristics were used to identify the isolated bacteria. An artificial infection experiment was carried out to assess the pathogenicity of isolated strains. Double PCR of Aeromonas hydrophila virulence genes was used to screen samples of M. chulae, Brachionus plicatilis, Artemia nauplii, and water. Results The dominant strain PYMc15 - 1 was isolated from diseased M. chulae. The characteristics (API ID32E) of PYMc15-1 corresponded to A. hydrophila. The gyrase subunit B (gryB) gene sequence of the strain possessed high similarity with those of A. hydrophila registered in GenBank. Phylogenetic tree analysis of Aeromonas based on the gryB gene showed that strain PYMc15-1 clustered together with A. hydrophila. The hemolysin ( hlyA) and gas lysin ( aerA) genes could be amplified from the strain PYMc15- 1, and the median lethal dose (LD₅₀ ) of PYMc15-1 to healthy M. chulae was 1. 2 × 10⁴ cfu / fish. Wild M. chulae, Artemia nauplii, and wild B. plicatilis were positive for pathogenic A. hydrophila, while the closed colony of M. chulae, indoor cultured B. plicatilis, and seawater samples were negative for pathogenic A. hydrophila. Conclusions A. hydrophila can naturally infect M. chulae. For wild M. chulae, living feeds are potential vectors of A. hydrophila. A. hydrophila should be tested when introducing M. chula and living feeds.

Abstract:Objective To investigate the regulatory effects of ferulic acid on hepatic steatosis and intestinal flora in hyperlipidemic mice. Methods Twenty-four 6-week-old male ApoE- / - mice were randomly divided into the control, model, ferulic acid [40 mg / ( kg·d)], and simvastatin groups [5 mg / ( kg·d)]; n = 6 per group. Six 6-week-old male C57BL/ 6 mice constituted the blank group. After 12 weeks of feeding a high-fat diet, the drugs were administered for another 12 weeks. The mouse feces were collected to detect the intestinal flora. Blood lipid levels were detected, and liver sections were prepared to observe the pathological changes. Results The body weight, serum total cholesterol ( TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) levels were much higher in the model group than in the control group ( P < 0. 05). Liver cells of the model group were full of lipid droplets, and most presented fatty degeneration. The amounts of Firmicutes and Erysipelotrichaceae in the model group were higher than those in the control group. Bacteroidetes, Ruminococcaceae and Odoribacter were decreased in the model group. Ferulic acid treatment significantly ameliorated the changes in body weight, serum TC, TG, and LDL-C ( P < 0. 05). Ferulic acid upregulated Firmicutes and Erysipelotrichaceae and downregulated Bacteroidetes, Ruminococcaceae and Odoribacter. Ferulic acid also alleviated the liver injury in the high-fat diet-fed ApoE- / - mice. Conclusions Ferulic acid improves dyslipidemia and hepatic steatosis, and regulates the intestinal flora imbalance.

Abstract:Objective To investigate the effects of electroacupuncture on NF-κB p65 expression in the spinal cord dorsal horn of rats with diabetic neuropathic pain. Methods Thirty SD rats were randomly divided into the normal and model groups. The rats in the model group were fed a high-fat and high-sugar diet for 5 weeks, then intraperitoneally injected with streptozotocin (STZ). The model diabetic neuropathic pain rats were further randomly divided into the diabetic neuropathic pain (DNP) model group and the diabetic neuropathic pain model + EA (DNP + EA) group. Two hertz of electroacupuncture was administered at the Zusanli and Kunlun ipsilateral acupoints for 7 consecutive days. Changes occurred in the fasting blood glucose, paw withdrawal threshold and paw withdrawal latency. Hematoxylin-eosin ( HE) staining was used to observe the morphological changes in the sciatic nerve in the rats, and western blotting was used to detect the NF-κB p65 protein expression in the spinal cord dorsal horn in rats. Results After 5 weeks on the high-fat and high-sugar diet followed by a single intraperitoneal injection of STZ, the fasting blood glucose increased, and the paw withdrawal threshold and latency decreased, indicating that the DNP model was successfully established. Electroacupuncture increased the paw withdrawal threshold and latency in the DNP rats but did not significantly affect the fasting blood glucose. HE staining result showed disordered arrangement of the myelinated nerve fibers, axonal swelling, uneven density of the myelin sheath and vacuolar degeneration of the sciatic nerve in the DNP rats. Electroacupuncture intervention did not significantly affect the sciatic nerve morphology in the DNP rats. Western blotting showed significantly increased NF-κB p65 protein expression in the spinal cord dorsal horn of the DNP rats, and electroacupuncture downregulated the NF-κB p65 protein expression in the spinal cord dorsal horn of the DNP rats. Conclusions Low frequency electroacupuncture has a good analgesic effect on the DNP model rats, possibly related to its inhibiting NF-κB p65 expression in the spinal cord dorsal horn.

Abstract:Objective To construct lymphocyte activation gene-3 ( Lag-3)-knockout mice and analyze the influence of Lag-3 knockout on mouse phenotypes to provide an animal model for subsequent Lag-3 in vivo function research. Methods Knockout mice were constructed via CRISPR/ Cas9 technology combined with microinjection of fertilized eggs. The Lag-3-knockout mice were screened via molecular identification and further verified via RT-PCR and flow cytometry. Lag-3 gene function in vivo was studied by establishing a ConA-induced liver injury model. Results PCR and product sequencing showed that exon 2-deleted Lag-3-knockout mice were obtained. The heart, spleen, lung and macrophages from ConA-induced homozygous mice were evaluated with only Lag-3 mRNA background expression signals detected in phagocytes and lymph nodes and only very low numbers of Lag-3-positive cells detected in mouse macrophages, spleen cells and lymph nodes. Phenotypic analysis revealed that deleting the Lag-3 gene significantly reduced the number of ConA-induced CD3⁺T cells in the peripheral blood, bone marrow and spleen as well as ConA-induced acute liver injury. Conclusions A Lag-3-knockout mouse model is successfully constructed. In vivo functional studies during liver injury show that Lag-3 deficiency significantly alleviated ConA-induced liver damage.

Abstract:Objective To establish and evaluate a mouse model of diabetic hindlimb ulcers, study the changes in blood flow and pathophysiology in mice with diabetic hindlimb ulcers, and explore the pathogenesis of the ulcers to provide a basis and reference for studying peripheral vascular diseases in diabetes. Methods ICR mice were divided into the diabetic hindlimb ulcer, hindlimb ischemia, and diabetic groups. Mice in the diabetic hindlimb ulcer and diabetes groups were intraperitoneally injected with streptozotocin to establish a model of type 1 diabetes. Mice in the diabetic hindlimb ulcer and hindlimb ischemia groups had their femoral arteries and veins ligated and their femoral artery severed. Sham surgery was performed in the diabetic group. Blood flow changes postoperation were detected via laser Doppler, and ischemic necrosis of the limbs was observed. Twenty-one days postoperation, hematoxylin and eosin staining was used to observe morphological changes in the ischemic tissue. Changes in CD31 and SMA expressions were analyzed. Results After the operation, the weight of the diabetic hindlimb ulcer group decreased significantly compared with that of the hindlimb ischemia group, and the hindlimb necrosis was more severe. Additionally, the diabetic hindlimb ulcer and hindlimb ischemia groups showed significantly decreased blood perfusion, which recovered gradually on days 3, 7, and 14 postoperation. Blood perfusion in the hindlimb ischemia group was near normal 21 days postoperation, but that of the diabetic hindlimb ulcer group decreased slightly. No significant change occurred in the diabetes group. In the diabetic hindlimb ulcer and hindlimb ischemia groups, muscle structure destruction and inflammatory infiltration occurred in the gastrocnemius tissues, and CD31 expression was increased. SMA expression was increased in the diabetic hindlimb ulcer and diabetes groups but not in the hindlimb ischemia group. Conclusions The diabetic hindlimb ulcer mouse model is successfully established. Limb necrosis and impaired recovery of blood perfusion are obvious in the diabetic hindlimb ulcer model compared with those of the hindlimb ischemia model. This model can be used to study the pathogenesis of diabetic vascular diseases and to screen therapeutic drugs.

Abstract:Objective To explore the mechanism of the ghrelin-GHSR pathway to alleviate obesity in hypoxic- exercise mice by observing ghrelin level changes in the gastric tissue and GHSR levels in the hypothalamic tissue. Methods Male C57BL/ 6J mice were randomly divided into the control group ( C, n = 8) or high-fat diet group ( H, n = 52) to establish the obesity model. After 8 weeks, the H group was further divided into the obese control group (HC), obese exercise group (HE), obese hypoxic exposure group (HH) and obese hypoxic exercise group (HHE). The HE and HHE groups were intervened by mid-intensity treadmill training while under intermittent hypoxic exposure ( 11. 2% oxygen). Weight and food intake were recorded weekly. Total cholesterol (TC), triglycerides (TG) and glucose levels in the serum were tested as well as the total ghrelin levels; the expression of GHSR mRNA in the hypothalamic tissue and ghrelin mRNA in the gastric tissue were detected via RT-PCR. GHSR and NPY in the hypothalamic tissue and the ghrelin, Goat and HIF- 2α protein expressions in the gastric tissue were detected via western blot after 4 weeks of intervention. Results (1) The HE, HH and HHE group weights were significantly lower than those of the HC group after intervention. In the initial stage of hypoxic intervention, the food intake decreased in the HH and HHE groups, and the food intake in the obese groups gradually became nearly the same as the intervention time increased. ( 2) The serum levels of the HC group were significantly higher than those of the C group; the TC level in the HH group significantly decreased, and the glucose levels in the HE, HH and HHE groups significantly decreased. The serum total ghrelin levels in the HH and HHE groups were significantly lower than those of the HC group. (3) Compared with the C group, the GHSR mRNA level in the hypothalamic tissue and the ghrelin mRNA level in the gastric tissue of the HC group were significantly decreased. The GHSR mRNA levels in the HH and HHE groups were significantly higher than those in the HC group. (4) In the hypothalamic tissue, the GHSR protein levels in the HE, HH and HHE groups and the NPY protein levels in the HE and HHE groups were significantly higher than those of the HC group. (5) In the gastric tissue, the ghrelin protein levels in the HE, HH and HHE groups, the Goat protein levels in the HE and HHE groups and the HIF-2α protein levels in the HH and HHE groups were significantly higher than those in the HC group. Conclusions Hypoxic training affects glucose and lipid metabolism by regulating the ghrelin-GHSR signaling pathway in the gastric tissue to control weight in obese mice.

Abstract:Objective To investigate the antioxidative protective effects of Eupolyphaga sinensis Walker (ESW) polypeptides on carbon tetrachloride (CCl4 )-induced chronic liver injury in mice. Methods Mice were randomly divided into the normal, model, ESW peptides ( 50, 100, 200 mg / kg) or positive drug groups. Mice in control group were intraperitoneally administred physiological salt solution. Mice in the ESW peptides group were intraperitoneally administered different doses of ESW peptides, and the positive drug group was intraperitoneally administered 100 mg / kg silymarin daily for 6 consecutive weeks. All mice except those in the normal group were intraperitoneally injected with 0. 1% CCl4 peanut oil solution (10 mL/ kg) twice weekly for 6 consecutive weeks. Twenty-four hours after the final administration, the mice were weighed and sacrificed, and their liver tissues were removed, processed and stained with hematoxylin and eosin to evaluate the changes in liver histology. Liver function enzymes (AST and ALT), antioxidant enzymes and peroxide (MDA) were detected via spectrophotometry. Inflammatory factors, apoptotic factors and fibrosis factor gene expression were determined via quantitative PCR. Enzyme-linked immunosorbent assay was used to assay inflammatory factor protein levels. Results No microscopic abnormalities were found in the liver cells of the normal group. In the model group, the hepatocytes showed hyperemia, necrosis and fibrosis, and the hepatic lobules had disappeared. The morphological structures of the hepatocytes in the ESW peptides group were damaged, but increasing the ESW peptide dose significantly lessened the degree of the injury, and the liver and spleen indices of these mice were significantly lower than those of the model group. Compared with the model group, the serum Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) enzyme activities and the MDA content in the livers of the mice in the ESW peptides group were significantly decreased. Additionally, the antioxidant enzyme ( SOD, CAT, GSH-Px ) activities were significantly improved, the inflammatory factor (IL-6, TNF-α, iNOS) protein and gene expression levels were significantly decreased, and the pro- apoptotic factor (Bax, Bcl-2, Caspase-3) and fibrosis factor (α-SMA, TGF-β) gene levels were significantly decreased and positively correlated with the ESW polypeptide dose. Conclusions ESW peptides attenuates CCl4 -induced chronic liver injury in mice, and these protective effects may be closely related to the peptides’ antioxidant effects.

Abstract:Objective To investigate the liver injury mechanism induced by D-galactose and L-glutamic acid in tree shrews. Methods Male tree shrews were randomly divided into four groups: the control (CT), D-galactose (D), L-glutamic acid (G) and D-galactose combined with L-glutamic acid (D+G) groups. The weight and survival rates were recorded weekly. Medication was administered for 8 weeks, then the tree shrews were sacrificed. Their livers were perfused with 4% paraformaldehyde for hematoxylin and eosin and immunohistochemical staining to detect TLR2, NF-κB and P- glycoprotein (P-gp) expressions. Results The body weights in the D+G group were lower at week 8 than at week 1. The survival rates in the G, D and D+G groups decreased compared with that of the CT group. Hepatocytic degeneration, edema, necrosis and inflammatory cell infiltration occurred in addition to dilatation of the central and portal vein and the branch bile duct in the livers of the G, D and D+G groups. Compared with CT group, the expressions of TLR2 ( P < 0. 05), NF-κB (P < 0. 01) and P-gp (P< 0. 01) were significantly increased in the D, G and D+G groups and were significantly higher in the D+G group than in the D or G groups. Conclusions D-galactose and / or L-glutamic acid induce liver tissue injury in tree shrews, which may be involved in activating TLR2 / NF-κB signaling and P-gp.

Abstract:Objective To observe the effects of five general anesthetics on cardiac electrical activity using a cardiac electrical implant in rats. Methods The anesthetic effect and cardiac electrical activity changes caused by five general anesthetics in rats were measured within 120 min before and after anesthesia using a cardiac electrical implant. Isoproterenol (0. 025 mg / mL) was administered to observe and compare the effects of the anesthetics on cardiac electrical activity in rats. Results Isoflurane and propofol acted quickly with stable anesthesia, fast recovery and minimal heart rate variations. Etomidate and ketamine acted quickly, but the anesthesia lasted a shorter time. Pentobarbital sodium acted slowly, and the anesthesia lasted longer, with a slow recovery and obvious inhibition of cardiac function. Propofol, etomidate, and pentobarbital sodium significantly reduced the effect of isoproterenol on the heart rate. Conclusions Isoflurane and propofol have the best anesthetic effect on the rats and least affected the heart rate. Isoflurane has the least effect on the isoproterenol-enhanced heart rate, suggesting that isoflurane is better suited for anesthetic operations and studying the effects of some cardiovascular active drugs on the heart rate.

Abstract:Objective AG129 mice have difficulty giving birth naturally, and conventional in vitro fertilization (IVF) reagents do not yield a sufficient number of embryos for transplantation. Reduced glutathione (GSH) was used to regulate a component of the IVF reagent and complete the IVF process in AG129 mice, presenting a potential method for biological purification and rapid reproduction of genetically engineered mouse strains with IVF difficulties. Methods Four experimental groups were designed using 0 mmol / L (control group), 0. 5 mmol / L, 1 mmol / L and 2 mmol / L of GSH for sperm capacitation and fertilization. Each group contained 5 superovulated mice, and the assay was repeated three times. Results The average fertilization rate differed between the GSH experimental groups and the control group (P< 0. 05). The 1 mmol / L GSH concentration had the best IVF effect on the AG129 mice. The average fertilization rate was (43. 35 ± 1. 76)%, and the embryo status was good. All recipient mice became pregnant and gave birth successfully after the embryos were transferred. Conclusions A GSH concentration of 1 mmol / L significantly improves the IVF efficiency of AG129 mice. This provides a potential solution for the biological purification and rapid propagation of mice with IVF difficulties.

Abstract:Objective A hand-made mouse restraint device was designed to establish an immobilization stress model for related stress experiments. Methods A centrifuge tube with a size suitable for the mouse body was used to prepare a mouse restraint device. The mouse restraint device was applied to maternal mice for 3 hours every day for 21 days starting 2 days after delivery to stimulate repeated immobilization stress. The maternal mice were separated from their offspring after delivery. Results In this postpartum mouse immobilization stress model, ghrelin expression was increased in the stomach, hypothalamus and serum, 5-HT₂ receptor expression was decreased, and depression-like symptoms, such as decreased exercise and offspring growth retardation, were observed. Conclusions A new device is constructed to establish an immobilization stress model in postpartum mice. Results from repeated experiments show good stability and reproducibility, suggesting that this model can be used to study immobilization stress in mice.

Abstract:As an important component of laboratory animals, the applied research of laboratory fish has expanded to all fields of bioscience, making significant contributions to scientific research. The standardization study of quality control of laboratory fish has encountered issues due to complications regarding the source, generation, breeding, and management of laboratory fish. This paper reviews the current situation regarding the breeding, management, and standardization study of closed colony and inbred strains of laboratory fish at home and abroad. The paper also analyzes current problems, aiming at providing references for the breeding, management, and standardization study of quality control of laboratory fish in China.

Abstract:As an important experimental subject, experimental fish play an increasingly important role in life science, medicine, and water environment safety evaluation. At present, domestic production and research teams of experimental fish are expanding rapidly; the use of experimental fish is increasing yearly. However, the quality of the experimental fish is inconsistent, which may have a serious impact on the result of scientific experiments. Therefore, there is an urgent need to formulate experimental fish quality control standards to regulate and guide their production. This paper reviews the quality control of experimental fish and its research status, and provides suggestions and references for the development of experimental fish quality control standards.

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.

Abstract:In recent decades, people are paying increasing attention to the welfare of experimental animals, and these animals are being integrated, coordinated and monitored when used in global scientific research. The “3Rs Principle” is the widely recognized and accepted core standard. Pharmacokinetic studies include essential animal experiments. Methods for protecting the welfare of experimental animals must be considered when the research reaches a certain stage and level. Researchers have gradually established and optimized intubation techniques on rodents (rats and mice), which can enable sampling blood from experimental animals while the animals are awake and moving freely. In this review, we searched the relevant literature and summarized the intubation surgical techniques used on rodents in pharmacokinetic studies to help protect the welfare of laboratory animals in China.

Abstract:Since the publication of special reviews and commentaries on zebrafish ( Danio rerio) in Science, Nature, and other journals in 1994, and completion of the whole genome sequencing of wild type (AB strain) zebrafish in 2009, the zebrafish has become a well-recognized new model organism. The remarkable advantages of zebrafish in the research and assessment of developmental toxicity and teratogenicity includes its transparency, high throughput, and rapid, high-efficiency, and low-cost screening. Zebrafish have been extensively used to screen the active components of traditional Chinese medicine for toxicological and pharmaceutical investigations, as well as for large-scale new drug screening of small molecule compounds. With the implementation of the " 3R principle (Reduction,Replacement,Refinement)" , the zebrafish has been proposed as an alternative animal model for developmental toxicity and teratogenicity tests. The recent progress of developmental toxicity and teratogenicity assessments in zebrafish is reviewed in this report.

Abstract:Zebrafish, a novel and well recognized model organism, has been widely used in many scientific fields, such as basic research, drug discovery, and development and environmental toxicology assessments, due to its low cost, high fecundity, external fertilization, short generation time, and transparency at early stages of development. In recent years, the zebrafish has emerged as a new type of vertebrate animal model for assessing nutrition, and biological functions. This article will introduce current uses of zebrafish in food science, including applications of zebrafish in the assessment of general and functional foods.

Abstract:Interstitial cystitis (IC), also known as bladder pain syndrome, is a common urological disease. As the IC pathogenesis is complex, no standard animal model has been established for the comprehensive and in-depth study of IC. Current IC models include intravesical infusion of chemical drugs, intraperitoneal injection of cyclophosphamide, autoimmune cystitis, neurogenic inflammation and psychological and physiological stressors/ natural models. Each model has advantages and disadvantages. This paper reviews the research progress on animal models of IC.