microRNA介导TNF-α基因SNP在PCOS胰岛素抵抗中的机制

多囊卵巢综合征(PCOS)是常见的生殖内分泌代谢紊乱疾病，由炎症因子引起的胰岛素抵抗(IR)是其重要病理环节。炎症因子与microRNA存在复杂的网络调控。本项目旨在研究肿瘤坏死因子α(TNF-α)基因SNP在PCOS-IR中的作用，明晰microRNA是否介导TNF-α基因SNP在胰岛素抵抗中起作用。我们前期研究证实TNF-αrs3179060C/T SNP位点与PCOS相关。本课题拟系统筛查TNF-α基因SNP多态位点，寻找与PCOS-IR相关SNP位点；以临床标本采用microRNA array、Northern blot等方法筛选并验证与PCOS-IR相关的microRNA,在此基础上筛选出1-2个受microRNA调控介导PCOS-IR的SNP并深入研究其对胰岛素信号通路IRS/PI3K/AKT/NFκB表达调控和生物学功能影响，为PCOS-IR防治提供新思路。

PCOS is the common reproductive endocrine metabolic disorder diseases. Local insulin resistance mediated by inflammatory factor in the ovary is the important pathological mechanism.However,the mechanism is not yet clear.Inflammatory factor and microRNA have complex regulation network. This project aims to study the role of tumor necrosis factor (TNF-α) gene SNP in PCOS-IR, and to make certain if microRNA mediates the TNF-α gene SNP function. In our previous studies, we confirmed that rs3179060C/T SNP sites of TNF-α was associated with PCOS.This study would systematically screen TNF-α gene SNP, and look for the SNP sites related with PCOS-IR;microRNA related with PCOS-IR would be analyzed using clinical biopsy by microRNA array;microRNA would be confirmed and then 1 or 2 SNP of PCOS-IR mediated by microRNA would be chosen.The biological functions on expression regulation would be further explored and the protein expression of IRS/PI3K/AKT/NFκB in the insulin signal pathway which is closely correlated insulin resistance,so as to provide new insights for the treatment and prevention of PCOS-IR.