Y-27632通过抑制ROCK通路降低内皮细胞中基质金属蛋白酶2和9表达  

Y-27632 reduces the MMP2 and MMP9 expression in endothelial cell via inhibition of ROCK signal pathway

作　　者：毛萧萧 周正翔 夏珂[1] 段琼[1] 赵伊遐[1] 杨达峰[1] 肖轶[1] 刘珍珍[1] 王雅[1] 杨天伦[1] 

机构地区：[1]中南大学湘雅医院心内科,长沙410008 [2]益阳医学高等专科学校,湖南益阳413000

出　　处：《中南大学学报（医学版）》2016年第6期566-570,共5页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(81570334);杨天伦教授的湘雅名医基金~~

摘　　要：目的:探讨ROCK通路抑制剂Y-27632对肿瘤坏死因子α(tumor necrosis factorα,TNF-α)诱导人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)基质金属蛋白酶2和9(matrix metalloproteinase 2 and 9,MMP2,MMP9)的表达与活性的影响。方法:体外培养原代HUVEC,分别予以TNF-α(25 ng/m L)、TNF-α+Y-27632(10μmol/L)处理24 h。Real-time PCR检测血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)、细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)、MMP2和MMP9 m RNA的表达水平;明胶酶谱检测MMP2和MMP9蛋白活性的改变情况。结果:与对照组相比,TNF-α明显上调ICAM-1,VACAM-1,MMP2,MMP9 m RNA的表达(P<0.01)和MMP2,MMP9的蛋白活性(P<0.05);与TNF-α处理组相比,Y-27632可显著抑制ICAM-1,VCAM-1,MMP2和MMP9 m RNA的表达(P<0.01),下调MMP2和MMP9的蛋白活性(P<0.05)。结论:Y-27632可以抑制TNF-α诱导的HUVEC炎症反应和MMP2,MMP9 m RNA和蛋白活性水平。Objective： To explore the effect of ROCK inhibitor Y-27632 on the matrix metalloproteinase 2 and 9 （MMP2 and MMPg） gene expression and activity in tumor necrosis factor a （TNF-α）-treated human umbilical vein endothelial cell （HUVEC）. Methods. HHUVEC was divided into 3 groups, a control group, a TNF-α group, and a TNF-αplus Y-27632 group. The expressions of vascular cell adhesion molecule-1 （VCAM-1）, intercellular adhesion molecule-1 （ICAM-1）, MMP2 and MMP9 were examined by real-time PCR. The MMP2/9 activity was measured by gelatin zymography. Results： Compared to the control group, the mRNA expressions ofICAM-1, VCAM-1, MMP2 and MMP9 were increased TNF-α-treated cells, which were suppressed by ROCK inhibitor （P〈0.01）. The MMP2/9 activity was elevated in TNF-α-treated cells, which was reversed by ROCK inhibitor （p〈0.0s）. Conclusion： ROCK inhibitor can suppress TNF-α-induced inflammation in endothelial cells through down-regulation of MMP2/9.

关 键 词：内皮细胞炎症 ROCK通路抑制剂 基质金属蛋白酶2 基质金属蛋白酶9 

分 类 号：R543.5[医药卫生—心血管疾病]