miR-32在多囊卵巢综合征高雄激素血症发病中的作用机制研究

多囊卵巢综合征（PCOS）是一种复杂的内分泌紊乱疾病，表现为高雄激素血症、稀发或不排卵、卵巢多囊样改变等，并有糖尿病、子宫内膜癌等多种远期风险，严重威胁女性健康。高雄激素血症在PCOS发病中起重要作用。我们前期研究发现PCOS患者和正常育龄妇女血清和颗粒细胞中存在差异表达的miRNA，并证实miR-32与高雄激素血症密切相关，且能影响颗粒细胞增殖与凋亡。本研究拟应用卵泡膜细胞、颗粒细胞原代培养、三维卵泡体外培养模型和PCOS大鼠模型，结合miR-32体内、外干扰和过表达技术，并通过targetscan分析、荧光素酶基因报告等方法分析miR-32靶基因，研究体内外miR-32对雄激素合成与代谢、卵泡发育与闭锁、颗粒细胞增殖与凋亡的影响及分子机制，以期更深入了解以miR-32及其靶基因为中心的调控网络在PCOS高雄激素血症发病中的作用，为临床治疗提供理论基础。

Polycystic ovarian syndrome (PCOS) is an endocrine disorder,affecting 5%-10% of women in the world. PCOS is characterized with hyperandrogenism, oligo/anovulation and polycystic ovary. Women with PCOS appear to be an increased risk for diabetes and endometrial cancer, which threats the health of female seriously. In our previous study, differentially expressed miRNAs are found in serum and granulosa cells in PCOS patients,compared with normal cycling women. It has been shown that miR-32 is associated with hyperandrogenism and the proliferation and apoptosis of granulosa cells. In the present study, we plan to study the mechanism of miR-32 on androgen synthesis in theca cells, and its effect on follicle development and atresia, proliferation and apoptosis of granulosa cells in vitro. Furthermore, we extend to explore the role of miR-32 and its target gene regulating net work in the hyperandrogenism of PCOS by targetscan analysis and miR-32 knockdown in vivo.