线粒体凋亡在子宫内膜异位症发病机制中的作用

The Role of Mitochondrial Apoptosis in Pathogenesis of Endometriosis

目的:探讨X染色体连锁的凋亡抑制蛋白(XIAP)、线粒体促凋亡因子线粒体蛋白Smac和肿瘤坏死因子(TNF-α)在子宫内膜异位症(EMT)发病机制中的作用。方法:免疫组化检测XIAP和Smac在55例正常子宫内膜(对照组)和65例卵巢子宫内膜异位囊肿(研究组)在位及异位内膜组织中的表达和相关性;流式细胞仪测细胞凋亡率;ELISA测两组患者腹水中TNF-a的表达。结果:①凋亡率:对照组分泌期高于增殖期(P<0.05);研究组在位及异位内膜中无周期变化(P>0.05);在位内膜低于正常内膜(P<0.05);异位内膜低于在位及正常内膜(P<0.05)。②XIAP的表达:在对照组和研究组在位内膜中增殖期均高于分泌期(P<0.05);在研究组异位内膜中无周期差异(P>0.05)。③Smac在对照组和研究组在位内膜中分泌期高于增殖期(P<0.05)。在异位内膜中无周期差异(P>0.05);Ⅲ期和Ⅳ期EMT患者异位子宫内膜中,Smac表达在增殖期与分泌期的比较,差异无统计学意义(P>0.05)。④腹水中TNF-α的表达:研究组高于对照组(P<0.05);Ⅲ期和Ⅳ期EMT患者腹水中TNF-α的表达差异无统计学意义(P>0.05)。⑤相关性:XIAP与Smac,Smac与TNF-α表达均成正相关(P<0.05)。结论:在卵巢子宫内膜异位症中,XIAP表达增强利于异位内膜种植生存,而线粒体蛋白Smac和TNF-α表达增强,又抑制其无限生长,表明线粒体凋亡在子宫内膜异位症的发病机制中可能扮演着重要的角色。

Objective：To study the role of X-linked inhibitor of apoptosis protein XIAP, mitochondrial proapoptotic factor Smac, and tumor necrosis factor alpha TNF-α in pathogenesis of endometriosis （EMT）. Methods：The expressions of XIAP and Smac of endometrium without EMT （ control, n = 55）, eutopic and ectopic endometrium with ovario-EMT （study group, n = 65） were investigated by immunohistochemical assay. Cell apoptosis rates were tested by flow cytometry. The expressions of TNF-α in peritoneal fluid of two .groups were measured by ELISA. Results： （1） Apoptosis rate in secretory phase was higher than follicular phase in control group （ P〈 0.05）, but there was not cyclic change in eutopic and ectopic endometrium in study group （ P〉 0.05）. Apoptosis rate in eutopic endometrium was lower than that in control, and apoptosis rate in ectopic endometrium was lower than that in both eutopic and con- trol endometrium （ P〈 0.05）. （2）The expression of XIAP during follicular phase was higher than secretory phase in both eutopic and control endometrium （ P 〈 0.05）. But there was no obviously cyclic difference in ectopic endometrium （ P〉0.05）. （3）The expression of Smac during secretory phase was higher than follicular phase in both eutopic and control endometrium （ P〈0.05）. But there was no obviously cyclic change in ectopic endometrium （P〉0.05）. （3）The expression of TNF-α in peritoneal fluid in study group was higher than that in control group （ P〈 0.05）, and there was no difference between stage TIT and IV. Signification correlations were found between XIAP and Smac, Smac and TNF-α. Conclusions： In ovado-endometriosis, the increased expression of XIAP is benefit for locally and distantly metastasic of ectopic endometrium. While overexpression of mitochondrial proapoptotic factor Smac and TNF-α restricted the growth of ectopic endometrium unlimited. So mitochondrial apoptosis play an important role in pathogenesis of endometdosis.