Fortunato S J, Menon R, Lombardi S J
Perinatal Research Center, Women's Health Research and Education Foundation, Nashville, TN, USA.
J Perinat Med. 1999;27(5):362-8. doi: 10.1515/JPM.1999.049.
We theorize that excessive degradation of the fetal membrane extracellular matrix (ECM) by specific matrix metalloproteinases (MMPs) results in preterm premature rupture of the membranes (PROM). Active, inhibitor free MMP2 and 9 (gelatinase A and B respectively) can degrade the amniochorion basement membrane Type IV collagen to initiate rupture. This study examines the levels of the gelatinases and their natural inhibitors (tissue inhibitor of matrix metalloproteinases-TIMPs) in the amniotic fluid during PROM, preterm labor (PTL) and at term.
A total of 51 AF samples were collected from the following groups of patients. Group 1: Women with PTL and no ROM (n = 16) Group 2: Women with PROM (n = 16) irrespective of labor status Group 3: Women at term with intact membranes undergoing cesarean delivery irrespective of labor status (n = 19). ELISA was used to assay MMP2, MMP9, TIMP1 and TIMP2 levels in the amniotic fluid. The active, TIMP free levels of MMP2 were quantitated by zymography followed by computerized densitometry. Active MMP9 was measured using a bioassay that specifically detects MMP9 activity. Statistical analysis was performed by Tukey-Kramer multiple comparison method.
PROM is associated with increased MMP2 levels (mean 2125 ng/ml;) when compared with term (mean 1455 ng/ml; p < 0.01) or PTL where a non significant increase was seen (mean 1862 ng/ml; p = ns). MMP9 levels were higher in PROM (mean 15.03 ng/ml) than at term (mean 1.14 ng/ml; p < 0.001) or PTL (mean 3.75 ng/ml; p < 0.01). TIMP1 levels were slightly increased during PROM (mean 3143 ng/ml) compared to term (mean 1892 ng/ml; p < 0.05) pr PTL where a non significant change was seen (mean 2406 ng/ml; p = ns). TIMP2 levels were decreased in PROM (mean 98 ng/ml) compared with term (mean 176 ng/ml; p < 0.05) and PTL (mean 236 ng/ml; p < 0.001). Active, TIMP free MMP2 levels were increased during PROM (mean 233 pg/ml) compared to those at term (mean 132 pg/ml; p < 0.05) or PTL (mean 132 pg/ml; p < 0.05). Active forms of MMP9 were seen only during PROM (mean 632 pg/ml).
Active, TIMP free forms of MMP2 and 9 are increased in the amniotic fluid of women with PROM. These MMPs can degrade the amniochorion basement membranes and other ECM components resulting in PROM.
我们推测特定基质金属蛋白酶（MMPs）对胎膜细胞外基质（ECM）的过度降解会导致胎膜早破（PROM）。活性、无抑制剂的MMP2和MMP9（分别为明胶酶A和B）可降解羊膜绒毛膜基底膜IV型胶原从而引发破裂。本研究检测了胎膜早破、早产（PTL）和足月时羊水明胶酶及其天然抑制剂（基质金属蛋白酶组织抑制剂-TIMPs）的水平。
从以下几组患者中总共收集了51份羊水样本。第1组：早产但未破膜的女性（n = 16）；第2组：胎膜早破的女性（n = 16），不考虑分娩状态；第3组：足月胎膜完整行剖宫产的女性，不考虑分娩状态（n = 19）。采用酶联免疫吸附测定法（ELISA）检测羊水中MMP2、MMP9、TIMP1和TIMP2的水平。通过凝胶酶谱法及计算机密度测定法定量检测无TIMP的活性MMP2水平。使用特异性检测MMP9活性的生物测定法测量活性MMP9。采用Tukey-Kramer多重比较法进行统计分析。
与足月（平均1455 ng/ml；p < 0.01）相比，胎膜早破时MMP2水平升高（平均2125 ng/ml），早产时虽有升高但无统计学意义（平均1862 ng/ml；p =无显著性差异）。胎膜早破时MMP9水平（平均15.03 ng/ml）高于足月（平均1.14 ng/ml；p < 0.001）或早产时（平均3.75 ng/ml；p < 0.01）。与足月（平均1892 ng/ml；p < 0.05）相比，胎膜早破时TIMP1水平略有升高，早产时无显著变化（平均2406 ng/ml；p =无显著性差异）。与足月（平均176 ng/ml；p < 0.05）和早产（平均236 ng/ml；p < 0.001）相比，胎膜早破时TIMP2水平降低。与足月（平均132 pg/ml；p < 0.05）或早产时（平均132 pg/ml；p < 0.05）相比，胎膜早破时无TIMP的活性MMP2水平升高（平均233 pg/ml）。仅在胎膜早破时可见活性形式的MMP9（平均632 pg/ml）。
胎膜早破女性羊水中无TIMP的活性形式的MMP2和MMP9增加。这些MMPs可降解羊膜绒毛膜基底膜及其他ECM成分，导致胎膜早破。
