BMP-9/Ca2+通路在PCOS胰岛素抵抗导致的卵泡膜细胞增殖中的作用及机制研究

胰岛素抵抗（IR）所导致的高雄激素血症以及卵泡膜细胞增殖，是多囊卵巢综合征（PCOS)妇女出现不孕的主要病理生理基础，近年来鲜有从保护因素为切入点探讨其调控机制及药物研发方向的相关研究，通过抑制胰岛素抵抗所导致的卵泡膜细胞增殖国内外更未见报道。我们前期实验发现，骨形成蛋白（BMP-9）作为2型糖尿病胰岛素抵抗的调控因子，可通过降低胰岛素抵抗时细胞内Ca2+的浓度，达到抑制卵泡膜细胞增殖的作用，且可能通过PI3K/AKT/mTORC1通路发挥作用。因此我们推测，BMP-9做为保护因素，可能通过降低卵泡膜细胞内Ca2+浓度，阻断PI3K/AKT/mTORC1信号通路，从而发挥抑制胰岛素抵抗所导致的卵泡膜细胞增殖作用。本实验拟通过临床观察、动物实验及功能机制实验，从抑制卵泡膜细胞增殖着手，进而改善PCOS患者胰岛素抵抗及高雄激素血症，有望为治疗PCOS不孕及一系列代谢异常提供理论依据。

Insulin resistance (IR) -induced follicle membrane cell proliferation is the main pathophysiological basis of infertility in polycystic ovary syndrome Insulin resistance (IR) -induced hyperandrogenism and theca cell proliferation are the main pathophysiological basis of infertility in women with polycystic ovary syndrome (PCOS). In recent years, few related research on protective factors to used in its regulation mechanism and direction of drug development and the proliferation of has not been reported. Our previous experiments found that bone morphogenetic protein (BMP-9 as a regulator of insulin resistance in type 2 diabetes can inhibit the proliferation of follicular membrane cells by reducing the intracellular Ca2 + concentration during insulin resistance, and possibly through PI3K / AKT / mTORC1 pathway plays a role. Therefore, we speculate that BMP-9 as a protective factor may block PI3K / AKT / mTORC1 signaling pathway by reducing the Ca2 + concentration in follicular membrane cells, thereby exerting inhibition of the proliferation of follicular membrane cells caused by insulin resistance. This experiment is to improve the insulin resistance and hyperandrogenism of PCOS patients by inhibiting the proliferation of follicular membrane cells through clinical observation, animal experiments and functional mechanism experiments, and is expected to provide a theoretical basis for the treatment of PCOS infertility and a series of metabolic abnormalities.