开展卵巢局部胰岛素抵抗（IR）研究可以为多囊卵巢综合征（PCOS）患者 IR的预防和治疗提供新的治疗靶点。本课题组前期工作已证实巨噬细胞极化异常参与了PCOS卵巢局部IR发生，但对于该过程巨噬细胞如何调节的机制尚不明确。本课题组最新研究证实去泛素化酶USP25参与了TLR3介导的巨噬细胞极化信号转导。申请者拟采用CHIP、凝胶电泳漂移、靶基因验证技术，利用体内动物模型及体外模型，以USP25/ TLR3为靶点，探讨从不同层面阻断及过表达USP25、TLR3、TRAF3对调节卵巢局部巨噬细胞极化改变参与卵巢局部糖代谢活性改变导致IR的机制。解析这些蛋白所参与的信息转导通路中上、下游关键基因的相互关系，探索USP25在PCOS卵巢局部IR形成中的作用及调控机制，旨在揭示PCOS卵巢局部IR发生的免疫学新机制，为PCOS的治疗提供新的研究思路和理论基础。

Studies focused on ovarian insulin resistance can be helpful to provide new target for prevention and treatment for PCOS patients. Immune abnormality can be the most importance cause for ovarian insulin resistance. Our previous work proved that macrophage polarity participated in ovarian insulin resistance of PCOS, but the inner mechanism remained unclear. Our recent study proved that USP25 involved in TLR3 receptor induced signal transduction in macrophage. We are aimed at exploring mechanism of ovarian local macrophage polarity in insulin resistance by down regulating and up regulating USP25, TLR3 and TRAF3 by immunoprecipitation, gel electrophoresis and targeted gene verification in vivo and in vitro. We are aimed at exploring relations among these targeted protein, upstream and downstream genes, revealing the inner mechanism of USP25 in development of ovarian insulin resistance and providing new insights and theory for treatment of PCOS patients.