胰岛素增敏剂对PCOS大鼠子宫内膜胰岛素受体底物表达的影响

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。

Effect of insulin sensitizer on the expression of insulin receptor substrate in endometrium of rats with polycystic ovarian syndrome

Objective To explore the expressions of insulin receptor substrate (IRS) 1, 2 and phosphorylation of tyrosine phosphokinase in the endometrium of rats with polycystic ovarian syndrome (PCOS) after metformin treatment. Methods The PCOS models were induced by Poretsky method and randomized to the model control group (n=20) and metformin group (n=20). A total of 10 SD rats were enrolled in the blank control group. The expressions of IRS-1, 2 and phosphorylation of tyrosine phosphokinase were analyzed with immunohistochemistry. Results The expressions of IRS-1, IRS-2, P-tyr(IRS-1) and P-tyr(IRS-2) proteins in the endometrium of the metformin group were significantly higher than those of the model control group (P<0.01), but still lower than those in the blank control group (P<0.05). Conclusion There is a selective insulin resistance in the endometrium of PCOS rats, which may be related to abnormal tyrosine phosphorylation and protein expressions of insulin receptor substrates. Metformin improves tyrosine phosphorylation and protein expressions of IRS-1and IRS-2 in the endometrium and partly corrects insulin resistance.