类固醇受体辅助活化因子-3通过PI3K/Akt/mTOR信号通路参与子痫前期发病机制中的作用研究  

Steroid receptor coactivator-3 is involved in the pathogenesis of preeclampsia by regulating PI3K/Akt/mTOR pathway

作　　者：袁雨[1] 单楠[1] 谭彬[1] 刘洋铭[1] 何承晋 漆洪波[1] 

机构地区：[1]重庆医科大学附属第一医院妇产科重庆医科大学"中国-加拿大-新西兰"联合母胎医学实验室,重庆400016

出　　处：《重庆医科大学学报》2017年第8期1034-1038,共5页Journal of Chongqing Medical University

基　　金：国家自然科学基金青年科学基金资助项目(编号:81601304)

摘　　要：目的:探讨类固醇受体辅助活化因子-3(steroid receptor coactivator-3,SRC-3)参与人脐静脉内皮细胞株(HUVECs)受损的信号通路,及其在子痫前期发病机制中的作用。方法:收集2014年10月至2015年10月在重庆医科大学附属第一医院行选择性剖宫产手术的正常足月妊娠组(31例)以及子痫前期组(29例)的胎盘组织。使用Western blot检测2组胎盘组织SRC-3的表达。脐静脉内皮细胞株(HUVECs)分为4个处理组:正常常氧对照(N)培养组、缺氧/复氧(H/R)培养组、SRC-3 sh RNA慢病毒敲降(sh SRC-3)培养组以及PI3K特异性抑制剂(LY294002)培养组。使用Western blot检测内皮细胞中SRC-3、p-Akt(Ser473)、Akt、p-m TOR(Ser2481)、m TOR的表达。使用细胞管腔成型实验检测内皮细胞血管形成能力。结果:SRC-3在子痫前期胎盘组织蛋白水平低于正常足月胎盘(t=3.501,P=0.013)。细胞学实验中,与N组相比,H/R组、sh SRC-3组及LY294002组HUVECs的SRC-3(t=4.236,P=0.007;t=5.469,P=0.002;t=4.165,P=0.008)、p-Akt(Ser473)/Akt(t=5.214,P=0.002;t=5.188,P=0.002;t=7.054,P=0.000)、p-m TOR(Ser2481)/m TOR(t=4.832,P=0.003;t=5.695,P=0.001;t=5.699,P=0.001)表达降低。H/R组、sh SRC-3组、LY294002组HUVECs血管形成能力低于N组(t=5.268,P=0.002;t=4.648,P=0.004;t=4.087,P=0.009)。结论:SRC-3可能通过PI3K/Akt/m TOR通路参与子痫前期的发病机制。Objective：To explore the mechanism of steroid receptor coactivator-3（SRC-3）involved in in the pathogenesis of preeclampsia（PE）. Methods：Western blot was used to detect the expression of SRC-3 protein in placentas. Cell treatments of each group were as follows：normal culture group（N）,hypoxia/reoxygenation（H/R） culture group,lentivirus short hairpin RNA against SRC-3transfect group（sh SRC-3）,PI3 K inhibitor LY294002 culture group（LY294002）. Western blot was used to detect the expression of SRC-3,p-Akt（Ser473）,Akt,p-m TOR（Ser2481）,m TOR protein in HUVECs. The tube formation assay was used to detect tube formation capacity of HUVECs. Results：The protein levels of SRC-3 were decreased in PE placentas than in normal placentas（t =3.501,P =0.013）. In four cell groups,the expression of SRC-3（t=4.236,P=0.007;t=5.469,P=0.002;t=4.165,P=0.008）,p-Akt（Ser473）/Akt（t=5.214,P =0.002;t =5.188,P =0.002;t =7.054,P =0.000）,p-m TOR（Ser2481）/m TOR（t =4.832,P =0.003;t =5.695,P =0.001;t =5.699,P =0.001）proteins in H/R group,sh SRC-3 group and LY294002 group were lower than that in normal group. Moreover,the tube formation ability of H/R group,sh SRC-3 group and LY294002 group were reduced（t=5.268,P=0.002;t=4.648,P=0.004;t=4.087,P=0.009）.Conclusion：These results suggest that SRC-3 may play a critical role in the pathogenesis of PE though PI3K/Akt/m TOR pathway.

关 键 词：子痫前期 类固醇受体辅助活化因子-3 血管内皮 PI3K/Akt/m TOR 

分 类 号：R714.24[医药卫生—妇产科学]