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目的探讨胰岛素增敏剂二甲双胍对多囊卵巢综合征(PCOS)大鼠子宫内膜胰岛素受体底物(IRS)1、2蛋白表达及酪氨酸磷酸化程度的影响。方法 Poretsky法建立PCOS大鼠模型,随机分为二甲双胍组和模型对照组,每组20只。空白对照组清洁级SD大鼠10只。采用免疫组织化学方法测定IRS-1和IRS-2蛋白在子宫内膜的表达及酪氨酸磷酸化程度。结果 3组大鼠子宫内膜腺上皮细胞均见IRS-1、IRS-2及酪氨酸磷酸化的表达。模型对照组子宫内膜腺上皮IRS-1、IRS-2、P-tyr(IRS-1)、P-tyr(IRS-2)表达水平明显低于空白对照组(P<0.01),二甲双胍组IRS-1、IRS-2、P-tyr(IRS-1)、P-tyr(IRS-2)表达水平显著高于模型对照组(P<0.01),低于空白对照组(P<0.05)。结论IRS-1和IRS-2蛋白在PCOS大鼠子宫内膜表达及酪氨酸磷酸化异常与胰岛素抵抗有关;胰岛素增敏剂二甲双胍可通过增加IRS-1和IRS-2蛋白的表达水平,提高酪氨酸磷酸化程度,部分改善PCOS大鼠子宫内膜胰岛素抵抗。
Objective To investigate the effect of insulin sensitizer metformin on endometrial insulin receptor substrate (IRS) 1,2 protein expression and tyrosine phosphorylation in rats with polycystic ovary syndrome (PCOS). Methods PCOS rat model was established by Poretsky method and randomly divided into metformin group and model control group, with 20 rats in each group. Blank control group of clean grade SD rats 10. The expression of IRS-1 and IRS-2 protein in the endometrium and tyrosine phosphorylation were determined by immunohistochemistry. Results The expressions of IRS-1, IRS-2 and tyrosine phosphorylation were all found in endometrial glandular epithelial cells of the three groups. The expression of IRS-1, IRS-2, P-tyr (IRS-1) and P-tyr (IRS-2) in endometrial gland epithelium of model control group was significantly lower than that of the blank control group 1, IRS-2, P-tyr (IRS-1) and P-tyr (IRS-2) were significantly higher than those in the model control group (P <0.01) and lower than those in the blank control group (P <0.05). Conclusion IRS-1 and IRS-2 protein expression in endometrial and tyrosine phosphorylation in PCOS rats is related to insulin resistance. Metformin, an insulin sensitizer, may be increased by increasing the expression of IRS-1 and IRS-2 protein Tyrosine phosphorylation, partially improve endometrial insulin resistance in PCOS rats.