基质金属蛋白酶-9及其组织抑制物-1诊断胎膜早破并绒毛膜羊膜炎的临床价值

目的:探讨母血、羊水、脐血中基质金属蛋白酶-9(MMP-9)及其组织抑制物-1(TIMP-1)的水平变化与胎膜早破发生的相关性,分析它作为一种新型的生物学标志物对绒毛膜羊膜炎和新生儿预后判断的临床价值。方法:采用双抗体夹心酶联免疫吸附法检测58例胎膜早破及38例正常孕妇(对照组)母血、羊水、脐血中MMP-9/TIMP-1水平的动态变化,同时进行胎膜的病理检查。结果:胎膜早破组母血、羊水、脐血中MMP-9的含量均高于对照组,尤以羊水中MMP-9水平升高明显,与对照组差异有显著性(P<0.05,P<0.01);而TIMP-1水平变化则明显低于对照组,差异有显著性(P<0.05,P<0.01)。母血、羊水、脐血中MMP-9的含量随破膜时间的延长增高,破膜时间超过24h增高尤为明显。而TIMP-1则随破膜时间的延长而下降,破膜时间超过24h降低尤为明显。绒毛膜羊膜炎患者母血、羊水、脐血中MMP-9水平明显高于非绒毛膜羊膜炎患者,差异有显著性(P<0.05,P<0.01),而TIMP-1水平则明显低于非绒毛膜羊膜炎患者,差异具有显著性(P<0.05,P<0.01)。胎膜早破组产妇所生新生儿Apgar评分≤7分者的母血、羊水、脐血中MMP-9的含量显著高于Apgar≥8分的新生儿(P<0.05,P<0.01),胎膜早破组新生儿Apgar评分≤7分者的母血、羊水、脐血中TIMP-1含量则显著低于Apgar≥8分的新生儿(P<0.05,P<0.01)。结论:MMP-9的异常升高及其抑制物TIMP-1显著下降是胎膜早破发生的重要发病机制。MMP-9/TIMP-1含量变化可以成为一种新的生物学标志用于早期诊断胎膜早破并绒毛膜羊膜炎特别是尚处于亚临床感染状态的孕妇,并有助于评估新生儿预后。

Clinical significance of MMP-9/TIMP-1 in patients with premature rupture of the membranes complicated with chorioamniotitis

Objective:To investigate the clinical roles of matrix metalloproteinase(MMP-9) and tissue inhibitors of matrix metalloproteinase(TIMP-1) in predicting premature rupture of the membranes(PROM) and chorioamnionitis.Methods:The levels of MMP-9 and TIMP-1 were detected by enzyme linked immunosorbent assay in maternal serum,amniotic fluid,umbilical cord serum of 58 pregnant women with PROM and 38 women with normal pregnancies.Chorioamnionitis was histopathologically confirmed after delivery.Results:The levels of MMP-9 were significantly higher and TIMP-1 were significantly lower in maternal serum,amniotic fluid,umbilical cord serum in patients with PROM than those of the control group(P<0.05,P<0.01).The longer the duration from rupture of membrances to delivery it was,the more serious chorioamnionitis it had,and the higher the levels of MMP-9 and the lower of TIMP-1 in maternal serum,amniotic fluid,umbilical cord serum were.The levels of MMP-9 were significantly higher and TIMP-1 were significantly lower in maternal serum,amniotic fluid,umbilical cord serum in patients with chorioamnionitis than those of non-chorioamnionitis(P<0.05,P<0.01).The levels of MMP-9 were significantly higher and TIMP-1 were significantly lower in maternal serum,amniotic fluid,umbilical cord serum in neonates whose Apgar score≤7 than those of neonates whose Apgar score≥8.Conclusion:PROM is associated with increased MMP-9 and decreased TIMP-1 levels.MMP-9 and TIMP-1 were the valuable clinical biological markers for identifying the chorioamnionitis and predicting neonatal prognosis.