17β雌二醇通过errα_pgc-1α通路抑制人肺动脉平滑肌细胞增殖

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1、授予单位代码10089学号或申请号20153187中国图书分类号R543.2HebeiMedicalUniversity硕士学位论文专业学位17β雌二醇通过ERRα/PGC-1α通路抑制人肺动脉平滑肌细胞增殖研究生：张树倩导师：袁雅冬教授专业：内科学二级学院：河北医科大学第二医院2018年3月目录中文摘要············································································1英文摘要································································

2、·············3英文缩写············································································5研究论文17β雌二醇通过ERRα/PGC-1α通路抑制人肺动脉平滑肌细胞增殖前言···········································································6材料与方法······································································7结果·········

3、·····································································14附图·············································································16附表············································································21讨论································································

4、·············23结论··············································································24参考文献···············································································24综述雌激素相关受体ERRα在呼吸系统疾病中的研究进展···············28致谢·······································································

5、············41个人简历············································································42中文摘要17β雌二醇通过ERRα/PGC-1α通路抑制人肺动脉平滑肌细胞增殖摘要目的：近年来研究显示，17β雌二醇（17βestradiol,E2）对肺血管具有重要的保护作用，主要通过雌激素受体α（estrogenreceptorα,ERα）介导，发挥抑制平滑肌细胞增殖的作用。雌激素相关受体α（estrogenrelatedreceptor,ERRα）是核受体亚族成员之一，与ERα具有高度同源性，能够

6、在不同细胞中和ERα在传导途径上通过其后与DNA结合位点及共激活因子之间的竞争性结合相互影响、相互作用，从而干扰雌激素-雌激素受体核内信号通路的传导。但ERRα是否参与介导E2对肺动脉高压的保护，目前仍无相关研究。本实验旨在探讨ERRα是否参与人肺动脉平滑肌细胞增殖的调控，明确ERRα是否介导低氧环境下E2对肺血管的保护作用。方法：培养人肺动脉平滑肌细胞（humanpulmonaryarterysmoothmusclecell,hPASMC）,随机分为常氧组、低氧组、低氧+XCT790（ERRα特异性反向激动剂）组和低氧+E2组。以CCK-8试剂检测各干预组细胞增殖情况；RT-PCR法测定

7、各组hPASMCs中ERR-α、PGC-1α、PCNA的mRNA水平；Westernblot法测定各组hPASMCs中ERR-α、PGC-1α、PCNA的蛋白表达水平。结果：CCK-8试剂检测结果显示低氧组细胞较常氧组增殖明显（P<0.05）,低氧+E2干预组和低氧+XCT790干预组细胞的增殖活性与低氧组相比明显被抑制（P<0.05）。RT-PCR、Westernblot检测到低氧组ERRα、PGC-1α及PCNA的m