明胶酶A及其特异性组织抑制剂在胎膜早破中的作用

The Role of MMP-2 and TIMP-2 in Fetal Membranes of Premature Rupture of Human Fetal Membranes

目的:通过检测自发性胎膜早破患者和正常分娩产妇及择期剖宫产产妇胎膜组织中明胶酶A(MMP 2)及其特异性组织抑制剂(TIMP 2) mRNA和蛋白质的表达,探讨明胶酶A及其特异性组织抑制剂在正常分娩前后和病理状态胎膜中的表达及其作用。方法:采用逆转录聚合酶链反应(RT PCR)和SP法对8例自发性胎膜早破患者、8例正常分娩产妇以及8例择期剖宫产产妇的胎膜组织中 MMP 2 和 TIMP 2 mRNA和蛋白的表达及定位进行检测。用光镜观察胎膜组织形态学特征的改变。结果: MMP 2 蛋白和mRNA在胎膜早破组表达明显高于正常分娩组和剖宫产组,两者比较,差异有显著性(P<0.05),而在正常分娩组的表达与剖宫产组比较差异无显著性 (P>0.05)。TIMP 2蛋白和mRNA在剖宫产组表达最高,正常分娩组次之,胎膜早破组最低,两两比较差异有显著性(P<0.05)。MMP 2在羊膜细胞内表达,在羊膜细胞的间叶细胞个别表达,强表达于绒毛膜的光滑的滋养细胞;TIMP 2表达于羊膜上皮细胞、网状细胞、绒毛膜滋养层。胎膜早破组的胎膜结构发生了明显改变。结论:胎膜早破组的胎膜中MMP 2的表达明显增高,而 TIMP 2 的表达明显降低,MMP 2 和 TIMP 2 的表达失调将导致胎膜基质的降解增加并最终导致胎膜的破裂。

Objective: To study the expression of MMP-2 and its inhibitor TIMP-2 in fetal membranes of premature rupture of human fetal membranes (PROM). Methods: Amniochorionic membranes were collected from the following groups as:group Ⅰ (women with spontaneous PROM before onset of labor, n=8), group Ⅱ (women with term labor after vaginal delivery, n=8) and group Ⅲ (women undergoing the selective cesarean section without the sign of infection or other complications of pregnancy,n=8). Messenger ribonucleic acid expression for MMP-2 and its specific inhibitor TIMP-2 were studied with the use of reverse transcriptase polymerase chain reaction (RT-PCR). MMP-2 and TIMP-2 peptides were localized by immunocytochemistry. The morphologic features of fatal membranes were studied with microscope. Results: The expression of MMP-2 in amniochorionic membranes from women between group Ⅱand Ⅲ had no statistically differences (P>0.05), but it was higher in group Ⅰ (P<0.05). The expression of TIMP-2 in group Ⅰ was lowest in three groups and it was lower in group Ⅱ than in group Ⅲ. There were statistically significant changes among the three groups (P<0.05). Immunocytochemistry demonstrated the presence of MMP-2 peptides in amnion and chorion leave trophoblasts. TIMP-2 was detected in both amnion and chorion and in cells of the rericular layer of the matrix. The morphologic features of fatal membranes changed significantly. Conclusion: Compared with that in group Ⅱ and Ⅲ, MMP-2 release increases and its inhibitor TIMP-2 decreases in PROM group, which could cause to increaseing of ECM degradation and weakening of the membranes, and lead to rupture.