米非司酮影响早孕滋养细胞的信号传导和凋亡的机制研究

目的　探讨米非司酮 (RU486 )在早孕滋养细胞信号传导及其凋亡中的影响。方法　 2 19例服用RU486早孕药物流产者 ,对其有效组 30例 ,失败组 2 3例 ,人流组对照 16例 ,以免疫组化法分别标记孕激素受体(PR)、雌激素受体 (ER)、表皮生长因子受体 (EGFR)、酪氨酸蛋白激酶C(αPKC)、分裂激活蛋白激酶 (MEK - 1)、细胞转化分裂介质 (raf- 1)和抗凋亡蛋白 (Bcl- 2 )。三组均计数凋亡指数 (AI)。有效组与失败组各 5例观察透射电镜下凋亡改变。结果　有效组PKC、raf- 1、MEK - 1、Bcl- 2的表达有明显抑制 (P <0 0 5 ) ;AI为 0 19%。失败组信号传导受抑主要为PR、ER和EGFR(P <0 0 1) ,AI为 0 11%。结论　RU486抑制早孕滋养细胞PKC信号通路及raf- 1瀑布激酶链和分裂激活蛋白 ,抑制增生分裂分化并诱导凋亡发生 ;而失败组可能在PR、ER和EGFR信号传导初始阶段发生受体介质功能紊乱和抑制

Research on the signals transduction and apoptosis of trophoblast cells in early pregnancy terminated by mifepristone

Objective To investigate the effects of RU486 on first trimester trophoblast cells in the events of signals transduction and apoptosis.Methods Of 219 early pregnancy women taking RU486,30 cases as effective group,23 cases as ineffective group and 16 cases as curette abortion group,and they were labeled immunohistochemically with PR,ER and EGFR,PKC,raf-1,MEK-1 and Bcl-2,respectively.The apoptotic phase syncytiocytes as apoptosis index(AI)in every group were counted.10cases of them(5 in effective group and 5 in ineffective one)were observed ultrastructurelly with the apoptosis by transmission electron microscopy.Results The signal mediators expressions of PKC,raf-1,MKE-1 and bcl-2 were restrained in the effective group(P<0 05),and AI value counted as 0 19%.But in ineffective group,the signals transductions were restrained at the primary stage on PR,ER,EGFR(P<0 01),AI value was 0 11%.Conclusion RU486 supressed the signals transduction of first trimester trophoblast cells on PKC and raf-1,MEK-1 central pathways,by which their proliferation and differentiaton were negatively affected,inducing them into the apoptosis program.But ineffective group showed inactivation in response to RU486 by the functional disorders and depression of recepter-mediators on PR,ER and EGF in primary stage.