p66shc调控PCOS卵巢纤维化病理的机理研究

项目名称： p66shc调控PCOS卵巢纤维化病理的机理研究

项目编号： No.81471422

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王勇

作者单位： 南京大学

项目金额： 73万元

中文摘要： 多囊卵巢综合征（PCOS）是最常见、最复杂的女性生殖内分泌疾病，临床主要表现为生殖激素紊乱，生殖功能障碍及糖代谢异常。其病因不明,最近文献表明，卵巢慢性炎症和氧化应激可能是PCOS病理进程的重要组成部分。我们的研究显示：PCOS动物模型存在以卵泡为中心的肌成纤维细胞增生和组织纤维化，是PCOS卵泡发育障碍，排卵受阻可能的原因。这种特征性组织纤维化起因虽不明确，但提示可能与卵泡发育异常有关。我们假设，与卵泡发育密切相关的TGF-β家族信号分子，如GDF-9和BMP-15等，因局部炎症和氧化应激过度激活，通过p66shc诱发或加重卵巢局部组织纤维化。我们提出，针对卵巢氧化应激和组织纤维化病理特征进行研究，确定其主要信号通路，为疾病药物干预，提供依据。

中文关键词： 多囊卵巢综合征；生殖内分泌；纤维化；氧化应激；慢性炎症

英文摘要： Polycystic ovary syndrome (PCOS), one of the most common and most complex female endocrinal diseases, is refractory to curative treatment due to lack of understanding about its etiology. Chronic inflammation and oxidative stress have recently been recognized as important components in the pathophysiology of PCOS, with the former being the most important factor that may lead to fibrosis. Previously, we found that DHEA-induced PCOS rats exhibited a high level of fibrosis in both ovarian and uterine tissues, which could be partially reversed by drugs such as metformin. Therefore, we speculate that in PCOS patients/animals, higher levels of local (ovarian and uterine) fibrosis and local and systemic oxidative stress (mediated by p66Shc) may exist. Fibrosis and oxidative stress might interact with each other, thus leading to anovulation and a higher rate of pregnancy loss in PCOS patients. In this project, we intend to explore the hypothesis and determine the mechanisms involved, and to develop therapeutic strategies to improve the function of ovaries/uteri of PCOS patients by inhibiting fibrosis or oxidative stress.

英文关键词： Polycystic ovary syndrome;reproductive endocrine;fibrosis;oxidative stress;chronic inflammation