小檗碱干预PCOS胰岛素信号通路关键分子作用机制研究

项目名称： 小檗碱干预PCOS胰岛素信号通路关键分子作用机制研究

项目编号： No.81503610

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 匡洪影

作者单位： 黑龙江中医药大学

项目金额： 18万元

中文摘要： 多囊卵巢综合征（PCOS）临床表现月经紊乱、不孕、高雄激素等生殖障碍，也表现糖脂代谢和胰岛素抵抗等代谢异常的“双重特征”。我们前期实验发现该“双重特征”也存在于PCOS的卵巢内。文献荟萃分析发现，小檗碱具有降糖、降脂和改善胰岛素抵抗等作用。本项目： （1）体内机制。小檗碱治疗对PCOS患者卵巢细胞胰岛素信号通路关键分子表达的活性调节、胰岛素抵抗/雄激素分泌过多等作用的卵巢内疗效；（2）体外实验。采用基因转染或小RNA干涉技术，运用Wester-Blot， Realtime PCR等方法，探讨胰岛素信号通路关键分子对体外培养卵巢细胞PCOS“双重属性”的关键病理作用以及小檗碱的调控。阐明胰岛素信号传导通路关键分子的活性异常是PCOS卵巢功能“双重属性”偶联的重要病理机制，也是小檗碱对PCOS疗效的重要机制。本项目体现前期基础实验-临床疗效评价和临床基础研究的转化医学要求。

中文关键词： 多囊卵巢综合征；小檗碱；胰岛素信号通路；卵巢细胞；高雄激素血症

英文摘要： Polycystic ovary syndrome(PCOS) is a very common and complex endocrine disease that affects 8% to 10% of women in reproductive age life.It is characterized by chronic anovulation,irregular menses and infertility,and symptoms of androgen excess,such as hirsutism and ache.In the long term,it increase the risk of type 2 diabetes,coronary heart disease,hypertensive disease,hyperlipidemia and other metabolic complications. In addition，the role of modern medicine for PCOS is poor.It seriously affects the reproductive function and physical and mental health.Although it’s mechanism entirely remains unclear,hyperinsulinemia and hyperandrogen may be two important foundations of pathophysiology. It is reported that abnormal glucose metabolism and insulin resistance presented in ovaries of patients with PCOS，and excessive androgen synthesis by the ovaries is the main source of hyperandrogenism. Therefore, ovarian dysfunction may be related to the PCOS incidence .In the study ，intended by the detection of abnormal expression and activity of insulin signaling pathway in ovarian granulosa cells of PCOS patients, as well as construction of insulin signaling pathway expression / interference vector and transfected target cells， to investigate the abnormal insulin signaling pathway expression and activity effect on glucose metabolism, hormones and ovarian signaling molecule in PCOS.To prove that abnormality of insulin signaling pathway is a risk factor of PCOS ，and berberine improve abnormal glucose metabolism and hormone levels in ovarian granulosa cells through the influence on insulin signaling pathway and glucose transporter，as well as their phosphorylation and then improve the systemic glucose metabolism abnormalities and hyperandrogenism of PCOS patients, basic experiment and randomized controlled clinical trial about berberine are done. The study will provide evidence of evidence-based medicine for the theoretical mechanism and Clinical application of berberine treatment on PCOS.

英文关键词： PCOS;berberine;insulin resistance;ovarian cell;Kaohsiung hormones