Ota Atsuyuki, Yonemoto Hisashi, Someya Akimasa, Itoh Shigeru, Kinoshita Katsuyuki, Nagaoka Isao
Departments of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, Japan.
J Soc Gynecol Investig. 2006 Dec;13(8):592-7. doi: 10.1016/j.jsgi.2006.10.001.
Increased proteolytic activities of matrix metalloproteinases (MMPs) such as MMP-3 and MMP-9 are associated with premature rupture of membranes at term. However, it is unclear whether MMP-2 is involved in the premature rupture of membranes. In this study, to elucidate the role of MMP-2, we evaluated the activity of MMP-2 and also the expression of pro-MMP-2, membrane type 1 (MT1)-MMP and tissue inhibitor of metalloproteinase (TIMP)-1 in premature rupture of membranes.
Amniochorions were prepared from 29 subjects with no labor (cesarean section; CS, n = 10), labor (normal delivery; ND, n = 10), and labor during premature rupture of membranes (PROM, n = 9). MMP-2 activity was spectrophotometrically assayed by measuring the digestion of an MMP-2-specific substrate. The levels of pro-MMP-2, MT1-MMP and TIMP-1 were determined by Western immunoblotting.
The activity of MMP-2 in PROM was significantly higher than that in CS and ND (P <.05). In addition, the levels of MT1-MMP, an activator of MMP-2, were higher in PROM than in CS and ND. In contrast, the level of TIMP-1, an inhibitor of MMP-2 was substantially lower in PROM than CS and ND. Moreover, the levels of pro-MMP-2 were increased more significantly in PROM and ND than in CS (P <.05).
Our results suggest that the increased expression of pro-MMP-2 and MT1-MMP and decreased expression of TIMP-1 may result in the increased activity of MMP-2, which is involved in the degradation of extracellular matrix (ECM) of fetal membrane, thereby inducing the premature rupture of membranes at term.
基质金属蛋白酶（MMPs）如MMP - 3和MMP - 9蛋白水解活性增加与足月胎膜早破有关。然而，尚不清楚MMP - 2是否参与胎膜早破。在本研究中，为阐明MMP - 2的作用，我们评估了MMP - 2的活性以及前MMP - 2、膜型1（MT1）-MMP和金属蛋白酶组织抑制剂（TIMP）-1在胎膜早破中的表达。
从29名未临产（剖宫产；CS，n = 10）、临产（正常分娩；ND，n = 10）和胎膜早破时临产（PROM，n = 9）的受试者中制备羊膜绒毛膜。通过测量MMP - 2特异性底物的消化情况，用分光光度法测定MMP - 2活性。通过蛋白质免疫印迹法测定前MMP - 2、MT1 - MMP和TIMP - 1的水平。
PROM中MMP - 2的活性显著高于CS和ND（P <.05）。此外，MMP - 2的激活剂MT1 - MMP的水平在PROM中高于CS和ND。相反，MMP - 2的抑制剂TIMP - 1的水平在PROM中显著低于CS和ND。而且，前MMP - 2的水平在PROM和ND中比CS中升高更显著（P <.05）。
我们的结果表明，前MMP - 2和MT1 - MMP表达增加以及TIMP - 1表达降低可能导致MMP - 2活性增加，MMP - 2参与胎膜细胞外基质（ECM）的降解，从而导致足月胎膜早破。
