改良超长方案改善PCOS合并胰岛素抵抗患者子宫内膜容受性机制的初步研究

项目名称： 改良超长方案改善PCOS合并胰岛素抵抗患者子宫内膜容受性机制的初步研究

项目编号： No.81501328

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 龚斐

作者单位： 中南大学

项目金额： 18万元

中文摘要： NF-κB通路活化诱导的子宫内膜胰岛素抵抗是PCOS合并胰岛素抵抗不孕患者子宫内膜容受性下降的原因之一。我们对PCOS患者应用改良超长方案的既往研究结果提示：改良超长方案（两次黄体中期使用GnRH-a）可能通过改善PCOS患者子宫内膜容受性而改善临床结局，但具体机制尚不清楚。亦有相关研究发现：GnRH-a作用于子宫内膜基质细胞降低NF-κB通路活性且呈时间、剂量依赖性。由此，本课题通过建立PCOS合并胰岛素抵抗动物模型应用GnRH-a、NF-κB诱导激酶RNAi腺病毒颗粒转染后并对PCOS合并胰岛素抵抗的不孕患者子宫内膜基质细胞应用GnRH-a、NF-κB抑制剂体外培养后，尝试了解GnRH-a是否通过降低人体子宫内膜NF-κB通路活性而调节子宫内膜胰岛素抵抗并最终改善子宫内膜容受性,为寻求辅助生殖技术药物治疗的分子靶点提供思路。

中文关键词： 多囊卵巢综合征；胰岛素抵抗；改良超长方案；；NF-κB；子宫内膜容受性

英文摘要： NF-κB pathway activation-induced endometrial insulin resistance was one of the causes of infertility patients with PCOS and insulin resistance whose endometrial receptivity is declined . Our previous findings indicated that the use of modified utral-long protocols ( GnRH-a was used twice in mid-luteal phaes) can improve clinical outcomes by improving endometrial receptivity in patients with PCOS , but the mechanism was not clear. Previous research also found that GnRH-a reduced the activity of NF-κB pathway in endometrial stromal cells and depended the dose and time. Thus, our subject will try to establish the animal model of PCOS and insulin resistance which applicate GnRH-a or transfect NF-κB inducing kinase RNAi adenovirus particles to explore the influence of NF-κB pathway activity 、the state of insulin resistance and embryo implantation rate ;then we will investgate GnRH-a whether reduce NF-κB pathway activity-induced insulin resistance and ultimately improve endometrial receptivity by using GnRH-a or the NF-κB inhibitor in endometrial stromal cells in infertility patients with PCOS and insulin resistance in vitro. Our research attempt to provide ideas for seeking inflammatory medication target in assisted reproductive technology in patients with PCOS by exploring the immune mechanism of GnRHa on improving the endometrial receptivity .

英文关键词： PCOS; insulin resistance;modified utral-long protocol; NF-κB;endometrial receptivity