MMP-1、PAR-1与子痫前期血管内皮损伤研究进展

THE RELATIONSHIP BETWEEN MMP-1,PAR-1 AND THEIR ROLES IN VASCULAR ENDOTHELIAL INJURY IN PREECLAMPSIA

MMP-1是基质金属蛋白酶家族成员之一,具有降解细胞外基质中的Ⅰ和Ⅲ型胶原的作用。活化的MMP-1可介导血管壁胶原组织重构,引起管壁通透性增加,水肿和蛋白尿形成。蛋白酶活化受体-1(PAR-1)属于G蛋白偶联受体家族成员,激活后可介导内皮细胞释放ET-1增多并激活Rho激酶通路。子痫前期病人外周血MMP-1表达增高,上调的MMP-1可激活内皮细胞表面PAR-1导致ET-1释放增多,造成血管舒缩功能紊乱、血压增高。此外,MMP-1表达增高导致血管内皮对Ang II等因子的反应性上调亦在子痫前期的病理改变中具有重要作用。

Matrix metalloproteinase- 1 is a member of the group of the matrix metalloproteinases with the capacity to cleave the type I and the type Ⅲ collagen. The enhancement in collagenolytic activity suggested by the actived form of MMP- 1 during preeclampsia strongly implys the alteration of the collagen network in the blood vessel wall. The damage to this network might increase vascular permeability and then result in edema and proteinuria. PAR- 1 is a member of the group of the G protein- coupled receptors,which is known to mediate the release of endothelin 1（ ET- 1） in endothelial cells and activate the Rho A kinase（ ROCK） pathway. In preeclampsia,the plasma concentration of MMP- 1is significantly greater than that in normal pregnancy,and MMP- 1 is an activator of protease- activated receptor 1,Activation of endothelial PAR- 1 also results in the release of endothelin 1（ ET- 1）,which is a potent vasoconstrictor and plays an important role in the injury of vascular endothelial cells and hypertension. Additionally,the increased circulating levels of MMP- 1 in preeclampsia also has the ability to enhance vascular reactivity to vasoconstrictor hormones such as Ang II,these effects may play a vital role in the pathogenesis of preeclampsia.