ERBB2/ERBB3在PCOS大鼠卵巢胰岛素抵抗发生中的作用及其机制研究

项目名称： ERBB2/ERBB3在PCOS大鼠卵巢胰岛素抵抗发生中的作用及其机制研究

项目编号： No.81200419

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 赵世斗

作者单位： 山东大学

项目金额： 23万元

中文摘要： 多囊卵巢综合征（PCOS）是育龄期妇女常见的内分泌代谢疾病，临床主要表现为月经异常、不孕、高雄激素征、卵巢多囊样改变等，且常伴有肥胖、胰岛素抵抗（IR）等代谢异常。目前研究表明PCOS患者卵巢本身存在糖代谢异常和IR，并且脱氢表雄酮诱导的PCOS大鼠存在卵巢局部胰岛素信号传导通路的异常，但肾上腺源性雄激素引起卵巢IR的具体机制还不清楚。我们的前期研究结果显示，ERBB2/3基因在PCOS大鼠卵巢组织中的表达明显升高。ERBB2/3基因的过高表达可能介导了PCOS大鼠卵巢IR的发生。本项目拟根据我们的前期研究结果，在动物模型和体外模型的基础上，利用实时定量RT-PCR、原位杂交、蛋白印迹、免疫组化和病毒感染等多种实验方法，研究ERBB2/3在卵巢IR发生中的作用及作用机制，并阐明胰岛素增敏剂及相应抑制剂对卵巢IR的治疗作用及机制，为PCOS的临床诊断、治疗及预防提供理论基础和实验依据。

中文关键词： 多囊卵巢综合征；ERBB2/ERBB3；胰岛素抵抗；高雄激素；颗粒细胞

英文摘要： Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disease affecting women of childbearing age, which is mainly characterized by abnormal menstruation, infertility, androgen excess and polycystic ovary, and often accompanied by metabolic disorders, such as obesity and insulin resistance (IR). Although it has been shown that abnormal glycometabolism and IR are present in the ovary of PCOS patient, and aberrant insulin signaling is present in the ovary of PCOS rat induced by dehydroepiandrosterone (DHEA), the definite mechanism of ovarian IR induced by adrenal androgen remains unclear. Our preliminary studies have shown that the expression of ERBB2/ERBB3 in the ovary of PCOS rat is significantly higher than that in the ovary of control rat, which may mediate the generation of ovarian IR in PCOS rat. On the basis of our previous results and in vivo and in vitro models, we use various experimental techniques, including real-time RT-PCR, in situ hybridization, Western blot, immunohistochemistry and viral infection, to investigate the role and mechanism of ERBB2/ERBB3 in ovarian IR, and furthermore, to explore the treatment effect of insulin sensitizers and corresponding inhibitors on ovarian IR and the underlying mechanisms. This study will provide experimental evidence and theoretical foundation for th

英文关键词： polycystic ovary syndrome；ERBB2/ERBB3；insulin resistance；high androgen；granulosa cell