高胰岛素血症与多囊卵巢综合征大鼠排卵障碍的相关性研究

Association between hyperinsulinema and ovulatory dysfunction in the rats with polycystic ovary syndrome

目的探讨高胰岛素血症参与多囊卵巢综合征(PCOS)排卵障碍的可能机制。方法(1)按改良Poretsky法建立PCOS动物模型,采用测定空腹血糖(FBG)、空腹胰岛素(FINS)、睾酮(T)、雌二醇(E2)、黄体生成素(LH)、卵泡刺激素(FSH),并计算胰岛素抵抗指数(HOMA1-IR);HE染色观察卵巢病理变化验证模型。(2)采用免疫组织化学方法检测卵巢组织生长分化因子9(GDF-9)蛋白质的表达。结果(1)与正常对照组比较,高胰岛素血症组FBG、FINS、T、HOMA1-IR显著升高(P<0.01)。(2)高胰岛素血症组各发育阶段卵泡数明显减少,但囊性扩张的卵泡和闭锁卵泡增多,卵泡膜细胞增生,卵泡间的间质明显增厚。(3)高胰岛素血症组卵巢组织GDF-9蛋白质表达显著低于正常对照组(P<0.05)。结论高胰岛素血症可能通过抑制GDF-9在卵巢组织的表达,使卵泡发育停滞、闭锁而导致排卵障碍。

Objectives： To study the effect of hyperinsulinemia on ovulatory dysfunction of the rats with polycystic ovary syndrome（PCOS）.Methods： Female SD rats aged 85 days were divided into two groups in pairs.The study group was given human chorionic gonadotropin for 9 days and insulin for 22 days.The control group followed the same procedure but normal saline was given instead.The levels of fasting blood glucose（FBG）,serum fasting insulin（FINS） and sex hormones in blood of both groups were detected.Ovarian follicles of two groups were counted by morphometric analysis and GDF-9 expression was investigated by immunohistochemistry.Results：（1） The levels of FBG,FINS and testosterone were significantly higher in study group than those in control group（P〈0.01）.（2）In contrast to the control group,the ovaries in study group demonstrated the higher ratio of follicular cysts with prominent thecal and interfollicular stromal proliferation.（3） The expression of GDF-9 protein in the ovaries of study group was significantly lower than that in control group（P〈0.05）. Conclusion： This study indicated that hyperinsulinemia inhibits follicular development,possibly through down-regulation of GDF-9 in the rat ovary,implying that GDF-9 may be involved in the pathogenesis of PCOS.