定坤丹对子宫内膜异位症大鼠PI3K/ AKT/ mTOR 信号通路的影响
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1.漯河医学高等专科学校第二附属医院妇产科,河南 漯河 462300;2.河南省中医药研究院附属医院妇科,郑州 450004

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R-33

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MiR-570-related lncRNA SNHG16 regulation of hepatoma cell resistance to sorafenib
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1.Obstetrics and Gynecology of the Second Affiliated Hospital of Luohe Medical College, Luohe 462300, China. 2.Department of Gynecology of the Affiliated Hospital of Henan Academy of Traditional Chinese Medicine, Zhengzhou 450004

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    摘要:

    目的 探索定坤丹对子宫内膜异位症(EMs)大鼠PI3K/ AKT/ mTOR 信号通路的影响。 方法 通过异位移植子宫内膜组织,构建EMs 大鼠模型,随机分为5 组:模型组(M 组)、定坤丹低(1. 13 g/ kg)剂量组(DKP-L组)、定坤丹中(2. 26 g/ kg)剂量组(DKP-M 组)、定坤丹高(4. 52 g/ kg)剂量组(DKP-H 组)、孕三烯酮(60 mg/ kg)组(GES 组),每组12 只,另取12 只正常SD 大鼠只开腹不异位移植子宫内膜组织,设为假手术组(Sham 组),以药物分组干预后处死大鼠,测定各组大鼠异位子宫内膜质量与体积,免疫组织化学染色检测大鼠异位子宫内膜微血管密度(CD31 阳性率)与VEGF、MMP-9 表达;酶联免疫吸附试验(ELISA)检测大鼠血清VEGF、MMP-9、iNOS、TNF-α水平;蛋白免疫印迹实验检测大鼠异位子宫内膜PI3K/ AKT/ mTOR 通路相关蛋白的表达。 结果 与Sham 组相比, M 组大鼠异位子宫内膜微血管密度、VEGF 与MMP-9 表达、血清VEGF、MMP-9、iNOS 及TNF-α 水平、异位子宫内膜织p-PI3K/ PI3K、p-AKT/ AKT、p-mTOR/ mTOR 明显升高(P<0. 05);与M 组相比,DKP-L、DKP-M、DKP-H 组大鼠异位子宫内膜质量与体积、异位子宫内膜微血管密度、VEGF 与MMP-9 表达、血清VEGF、MMP-9、iNOS 及TNF-α 水平、异位子宫内膜p-PI3K/ PI3K、p-AKT/ AKT、p-mTOR/ mTOR 均降低,且DKP-L、DKP-M、DKP-H 组之间呈剂量依赖性(P<0. 05);DKP-H 组和GES 组相比,大鼠各指标无明显差异(P>0. 05)。 结论 定坤丹可减轻炎症,抑制EMs大鼠异位内膜生长,可能是通过阻断PI3K/ AKT/ mTOR 信号途径传导实现的。

    Abstract:

    Objective To explore the effect of Dingkun pill on the PI3K/ AKT/ mTOR signaling pathway in rats with endometriosis (EM). Methods EM rat models were established by heterotopic transplantation of endometrial tissue and randomly divided into five groups: model group (M group), Dingkun pill low (1. 13 g/ kg) dose group (DKP-L group), Dingkun pill medium (2. 26 g/ kg) dose group (DKP-M group), Dingkun pill high (4. 52 g/ kg) dose group (DKP-H group) and gestrinone (60 mg/ kg) group (GES group) with 12 rats in each group. The abdomen was opened without transplantation of ectopic endometrial tissue in another 12 normal SD rats as sham operation group (Sham group). The rats were sacrificed after drug treatments, The mass and volume of ectopic endometrium were measured. The microvessel density (CD31-positive rate) and expression of VEGF and MMP-9 in rat ectopic endometrial tissue were assessed by immunohistochemical staining. Rat serum VEGF, MMP-9, iNOS and TNF-α levels were measured by enzymelinked immunosorbent assays. Expression of PI3K/ AKT/ mTOR pathway-related proteins in rat ectopic endometrial tissue was detected by Western blot. Results Compared with those in the sham group, the microvessel density, VEGF and MMP-9 expression, serum VEGF, MMP-9, iNOS and TNF-α levels, p-PI3K/ PI3K, p-AKT/ AKT and p-mTOR/ mTOR in ectopic endometrial tissue were significantly increased in the M group (P<0. 05). Compared with the findings in the M group, the ectopic endometrial volume, weight of the ectopic lesion, microvessel density of the ectopic endometrial tissue, VEGF and MMP-9 expression, serum VEGF, MMP-9, iNOS and TNF-α levels, p-PI3K/ PI3K, p-AKT/ AKT, and pmTOR/ mTOR in ectopic endometrial tissue were all decreased in the DKP-L, DKP-M, DKP-H groups, and dosedependent effects were observed in Dingkun pill low dose, Dingkun pill medium dose, and Dingkun pill high dose groups(P<0. 05). Compared with DKP-H group and GES group, no significant difference was found in the indicators (P>0. 05). Conclusions Dingkun Dan reduces inflammation and inhibits ectopic endometrial growth in EM rats, which may be achieved by blocking the PI3K/ AKT/ mTOR signal pathway.

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王伟伟,席 鑫.定坤丹对子宫内膜异位症大鼠PI3K/ AKT/ mTOR 信号通路的影响[J].中国比较医学杂志,2023,33(12):55~61.

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  • 收稿日期:2023-02-17
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  • 在线发布日期: 2024-01-22
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