子宫内膜缺血在子宫内膜异位症中的作用及分子机制  

Effects and molecular mechanisms of endometrial ischemia in endometriosis

作　　者：王敬华[1] 祁建青[1] 尤莉芳[1] 吴宏宇[1] 卢艳阳[1] 任琼珍[1] 

机构地区：[1]江苏苏州市第七人民医院,苏州215151

出　　处：《生殖医学杂志》2015年第6期470-476,共7页Journal of Reproductive Medicine

基　　金：苏州市科技局项目(课题号SYS201268)

摘　　要：目的探讨子宫内膜缺血在子宫内膜异位症发生中的作用及分子机制。方法选择SPF级,8~10周龄雌性C57BL/6小鼠,建立子宫内膜缺血预处理（IPC）以及缺血（ISCH）模型。根据供体小鼠处理方式分为对照组（CON组）、预缺血处理组（IPC组）、缺血处理组（ISCH组）、ISCH＋IPC组以及Akt抑制剂预处理的ISCH＋IPC组（ISCH＋IPC＋LY组）;采用HE染色检测异位移植内膜病灶大小,TUNEL法测定细胞凋亡指数,RT-PCR测定子宫组织Akt、Bcl-2以及Bax基因表达,Western blot检测子宫组织p-Akt、Bcl-2以及Bax蛋白表达。结果 （1）IPC组成模率高于CON组（P〈0.05）,IPC＋ISCH组成模率以及内膜存活率均高于ISCH组（P〈0.05）。（2）CON组细胞凋亡指数（AI）与IPC组差异无统计学意义（P〉0.05）;IPC＋ISCH组AI低于ISCH组但高于IPC组,差异均有统计学意义（P〈0.05）。（3）RT-PCR显示,IPC组Akt-mRNA、Bcl-2-mRNA以及Bax-mRNA表达均高于CON组（P〈0.05）;ISCH组及IPC＋ISCH组Akt-mRNA、Bcl-2-mRNA表达均低于IPC组,而Bax-mRNA表达高于IPC组（P〈0.05）;IPC＋ISCH＋LY组Akt-mRNA、Bcl-2-mRNA表达低于IPC＋ISCH组,而Bax表达高于IPC＋ISCH组（P〈0.05）。（4）Western blot显示,IPC组p-Akt、Bcl-2及Bax蛋白表达高于CON组（P〈0.05）;ISCH组p-Akt、Bcl-2蛋白表达低于IPC组（P〈0.05）,IPC＋ISCH组p-Akt、Bcl-2蛋白表达高于ISCH组、而Bax蛋白表达低于ISCH组（P〈0.05）;IPC＋ISCH＋LY组p-Akt、Bcl-2蛋白表达低于IPC＋ISCH组（P〈0.05）,而Bax蛋白表达高于IPC＋ISCH组（P〈0.05）。结论子宫内膜预缺血处理能够抑制异位移植后内膜细胞凋亡,而这一机制可能与Akt信号通路磷酸化以及上调其下游靶蛋白Bcl-2、下调Bax有关。Objective： To investigate the role and molecular mechanisms of endometrium ischemia in endometriosis.Methods：The female C57BL/6mice of SPF level with 8-10 weeks old were selected for establishing ischemic preconditioning（IPC）and endometrial ischemia（ISCH）model.The mice were divided to control group,IPC group,ISCH group,ISCH ＋IPC group and ISCH ＋IPC＋LY（treated by LY294002（Akt inhibitor）（group according to the treatment mode.The lesion size was detected by HE staining.The apoptosis index was assayed by TUNEL.The expressions of Akt,Bcl-2and Bax gene in uterine tissue were determined by RT-PCR,and the expressions of p-Akt,Bcl-2and Bax proteins were detected by Western blot.Results：The success rate of establishment of IPC model was significantly higher than the control group（P〈0.05）.The success rate of model establishment and endometrial survival rate were significantlyhigher in IPC＋ISCH group than those in ISCH group（P〈0.05）.The apoptosis index（AI）was not significantly different between control group and the IPC group（P〉0.05）,and the AI in IPC＋ISCH group was significantly lower than ISCH group,but higher than IPC group（P〈0.05）.The results of RTPCR showed that the mRNA expressions of Akt,Bcl-2and Bax in IPC group were significantly higher than those in the control group（P〈0.05）.The mRNA expressions of Akt,Bcl-2were significantly lower but Bax significantly higher in ISCH group or IPC＋ISCH group than those in the IPC group（P〈0.05）.The mRNA expressions of Akt,Bcl-2were significantly lower,but Bax significantly higher in IPC＋ISCH＋LY group than those in IPC＋ISCH group（P〈0.05）.The results of Western blot showed that the protein expressions of p-Akt,Bcl-2and Bax were significantly higher in IPC group than those in the control group（P〈0.05）.The protein expressions of p-Akt,Bcl-2protein expression were significantly lower than those in the IPC group（P〈0.05）.The protein expressions of p-Akt,Bcl-2 were significantly higher,but Bax

关 键 词：子宫内膜缺血 子宫内膜异位症 AKT BCL-2 抗凋亡 

分 类 号：R[医药卫生]