细胞凋亡与胎膜早破的相关性研究

目的:探讨细胞凋亡增加是否为胎膜早破的一个发病机理或危险因素。方法:随机采集临产前剖宫产分娩的初产妇肘静脉血、羊水及胎膜,其中胎膜早破者34例,正常完好胎膜17例。①用ELISA测定各组血清、羊水中TNF-α的浓度:②用TUNEL原位标记术精确测定各组胎膜细胞凋亡指数;③用免疫组化法检测各组胎膜组织中Bax、Bcl-2、Fas、Caspase-3表达情况。结果:①胎膜早破组血清、羊水中TNF-α浓度明显高于正常对照组水平(P<0.001);且血清、羊水中TNF-α浓度有相关性,r=0.386。胎膜感染组血清、羊水中TNF-α浓度较无感染组高(P<0.001)。②胎膜早破组胎膜感染发生率高于对照组(P<0.05)。③胎膜早破组细胞凋亡指数明显高于正常组(P<0.001);感染组细胞凋亡指数较无感染组高(P<0.001)。④胎膜早破组促凋亡蛋白Bax、Fas、Caspase-3阳性表达率高于对照组(P<0.05),但抑凋亡蛋白Bcl-2阳性表达率两组间无统计学差异(P>0.05);胎膜感染组Bax、Bcl-2、Caspase-3阳性表达率与无感染组比较无统计学差异(P>0.05),但感染组Fas阳性表达率高于无感染组(P<0.05)。结论:基因、环境因素相互作用下的细胞凋亡增加可能是胎膜早破的一个重要发病机制,可独立致病,亦或与其他相关危险因素(如感染)协同致病。

Correlative Study on Apoptosis and Premature Rupture of Fetal Membranes

Objective: To explore whether the increased apoptosis in fetal membranes is a pathogenesis or a risk factor of premature rupture of membranes (PROM). Methods: The antecubital venous blood, amniotic fluid and amniochorion (fetal membrane) samples were collected from 51 nulliparous women undergoing cesarean delivery before the onset of labor, including 34 cases of PROM and 17 cases of term intact membranes as controls. (1) the levels of TNF-α in serum and amniotic fluid were assayed by ELISA; (2) TUNEL technology was used to label in situ apoptotic cells to detect exactly apoptosis index in fetal membranes; (3)The expressions of Bax, Bcl-2, Fas, Caspase-3 in fetal membranes were determined by immunohistochemistry. Results: (1)The mean serum and amniotic concentrations of TNF-α fluid were significantly higher in patients with PROM than in controls (P<0.001). Amniotic fluid TNF-α levels were positively correlated with serum TNF-α (r-=0.386, P=0.005). TNF-α levels in serum and amniotic fluid were significantly higher in the infectious group than in the noninfectious group (P<0.001). In the noninfectious group, patients with PROM had a significantly higher mean concentrations of TNF-α in serum and amniotic fluid than the control group (P<0.01); (2) Fetal membranes histology indicated: subclinical infection cases and mean apoptosis index in the PROM group were significantly higher than that in the control group (P<0.05, P<0.001);(3)Cellular apoptosis index was significantly higher in the infectious group compared with the noninfectious group (P<0.001). In the noninfectious group, patients with PROM had a significantly higher mean apoptosis index than the control group (P<0.001); (4)The positive expression rates of proapoptotic-proteins Bax, Fas, Caspas-3 in fetal membranes of the PROM group were significantly higher than control group (P<0.05). whereas antiapoptotic-protein Bcl-2 expression between two groups was not significant (P>0.05). There were no significant differences in Bax, Bcl-2, Caspase-3 expression between the infectious and noninfectious groups. In contrast, a statistically significant increase was noted in Fas expression from the infectious group compared with the noninfectious group (P<0.05). Conclusion: The increased apoptotic cells by gene-enviroment interaction appear to play a significant role in the pathogenesis of PROM, and increased apoptosis in membranes may be a single risk factor or take cooperative effect together with other associated risk factors, such as infection.