环境内分泌干扰物AGEs在多囊卵巢综合征发病机制中的研究

项目名称： 环境内分泌干扰物AGEs在多囊卵巢综合征发病机制中的研究

项目编号： No.81471424

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： 刘伟

作者单位： 上海交通大学

项目金额： 67万元

中文摘要： 近年，随着生活水平的提高、饮食结构的改变等，高级糖化物终末产物(AGEs)摄入较前显著增加。与之相伴的是：女性肥胖和多囊卵巢综合征（PCOS）的发病率逐年升高。PCOS是造成育龄妇女不孕不育最主要的病因之一，还显著增加糖尿病和冠心病等疾病的发病风险。研究发现AGEs-RAGE系统与胰岛素抵抗（IR）和女性高雄激素血症(HA)密切相关，而IR和HA正是PCOS的两大核心病理生理改变。 我们发现PCOS患者血AGE水平显著高于对照，而AGEs-RAGE系统在PCOS发病中的作用及其机制仍未阐明。我们拟在本课题中通过：横断面调查、动物和细胞学实验，系统的研究：1)环境因素（如饮食结构）对血和卵泡液中AGEs、RAGE水平的影响；2）AGEs-RAGE系统异常导致IR和PCOS发病的分子机制；3）探索减少AGEs水平的可能途径和AGE-RAGE系统的有效阻断剂，为PCOS的防治提供新的视角和途径。

中文关键词： 环境内分泌干扰物；多囊卵巢综合征；胰岛素抵抗；高雄激素血症；高级糖基化代谢产物

英文摘要： In recent years, with the improvement of living conditions and changes of diet structure, advanced glycosylation end products(AGEs) intake has been increased significantly. Polycystic ovary syndrome(PCOS) is one of the major causes of infertility in the reproductive-aged women. Most of the patients with PCOS have metabolic abnormalities such as diabetes and cardiovascular disease.Studies have found that AGE-RAGE system is closely related to insulin resistance and hyperandrogenemia, which are two core pathophysiological processes in PCOS. In our previous study, it has been found the AGEs levels in the PCOS patients were higher than that of controls. However, the role of AGE-RAGE system in the pathyphysiology of PCOS are still unclear. Therefore, the aim of this study is to investigate: 1)the effects of environmental factors such as diet structure on the levels of AGEs and RAGE in the plasma and follicular fluid; 2) the potential molecular mechanism of AGE- RAGE system dysfunction in insulin resistance and PCOS, 3) the potential pathways to decrease the level of AGEs, and efficient blockers of the AGE-RAGE system. The outcome of this study will provide the new perspective approach for the prevention and treatment of PCOS.

英文关键词： environmental endocrine disruptors;polycystic ovary syndrome;insulin resistance;hyperandrogenemia;advanced glycosylation end productions