MMP-1/TIMP-1在人及裸鼠异位内膜组织中的表达及其与雌、孕激素的关系

目的 探讨 MMP-1/TIMP-1在子宫内膜异位症发病机制中的作用及雌、孕激素对二者表达的影响.方法 采用RT-PCR及SP免疫组化法检测异位内膜组织(35例)、内异症患者正位内膜(22例)及正常子宫内膜组织(28例)中MMP-1/TIMP-1mRNA及蛋白的表达:建立裸鼠子宫内膜异位症模型并予体外雌、孕激素干扰,随机分成四组雌激素(E)组、孕激素(P)、E+P组、及对照组],观察不同激素干扰下裸鼠内异症模型的种植成功率及其大体、镜下形态表现;采用免疫组化方法检测MMP-1/TIMP-1蛋白在不同组别裸鼠异位内膜中的表达.结果 (1)四组裸鼠内异症模型均见种植物成活,总种植成功率为86.4%(51/59),各组间成功率无显著差异.其中P组种植物数量较其他组明显增多,P组、E+p组种植物明显大于E组、对照组.受外源性雌孕激素影响,镜下种植物分别呈现增殖期和分泌期特点.(2)MMP-1/TIMP-1 mRNA及蛋白在人及各组裸鼠异位内膜组织中均有表达,其中MMP-1相对表达量均明显高于正常子宫内膜,差异显著(P<0.05);TIMP-1表达与正常内膜组织无显著差异,各组MMP-1/TIMP-1比值均显著高于正常子宫内膜组(P<0.01);(3)内异症正位内膜组织中MMP-1/TIMP-1 mRNA及蛋白表达比值均高于正常对照组;(4)裸鼠E组、E+P组MMP-1蛋白表达均明显高于C组,而P组与C组间无差别;TIMP-1蛋白在C组的表达明显高于其他激素干扰组.结论 (1)裸鼠模型是Ems早期临床研究的理想模型;(2)MMP-1/TIMP-1在人及裸鼠异位组织中异常表达,动态平衡紊乱,在Ems的发生发展中起重要作用;(3)在位内膜组织具有较强的侵袭性,可能是异位内膜发生种植的源头因素.

Expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in human and nude mouse ectopic endometrium and the effect of estrogen and progestin on their expression

Objective To explore the roles of matrix metalloproteinase-1(MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the pathogenesis of endometriosis and the effects of estrogen and progestin on their expression.Methods Immunohistochemistry and RT-PCR were employed to detect the expression of MMP-1 and TIMP-1 in the ectopic tissues of 35 patients with endometriosis,22 eutopic endometrium tissues from women with endometriosis and 28 normal controls.Fifty-nine nude mice were injected with human late s...