缬沙坦对人脐动脉平滑肌细胞MMP-9、TIMP-1表达的影响——附106份检测报告  

The influence of valsartan on expression of MMP-9 and TIMP-1 in human umbilical artery smooth muscle cell

作　　者：查政[1] 张清华[2] 蒋知新[2] 林虎[2] 梁雪梅[2] 

机构地区：[1]南方医科大学研究生学院,在读博士生510515 [2]解放军305医院老年病中心

出　　处：《新医学》2009年第3期154-158,共5页Journal of New Medicine

基　　金：全军医药卫生"十五"计划课题(04LX048);全军医药卫生"十一五"计划科技攻关课题(06G144)资助

摘　　要：目的:探讨缬沙坦对人脐动脉平滑肌细胞基质金属蛋白酶-9(matrix metal-loproteinase,MMP-9)、组织型金属蛋白酶抑制物-1(tissue inhibitor of metalloproteinase,TIMP-1)表达的影响。方法:对人脐动脉平滑肌细胞进行原代培养,根据平滑肌原代细胞的培养方式分为氧化低密度脂蛋白(oxidized low-density lipoprotein,ox-LDL)培养组(ox-LDL组)、AngⅡ加ox-LDL培养组(AngⅡ组)、AngⅡ加ox-LDL加缬沙坦培养组(缬沙坦组)、普通培养基培养组(对照组),应用ELISA法及逆转录PCR法分别检测4组上清液中的MMP-9、TIMP-1含量,以及细胞内MMP-9、TIMP-1 mRNA的相对表达量,并应用统计学方法进行比较。结果:AngⅡ组上清液中的MMP-9含量均明显高于其他3组(均为P<0.01)。ox-LDL组与AngⅡ组上清液中TIMP-1的含量均明显低于对照组(均为P<0.01),缬沙坦组与对照组上清液中TIMP-1的含量比较差异无统计学意义(P>0.05)。另外,AngⅡ组细胞内MMP-9mR-NA的相对表达量均明显高于其他3组(均为P<0.01),其TIMP-1 mRNA的相对表达量均明显低于对照组、ox-LDL组及缬沙坦组(均为P<0.01),缬沙坦组细胞内TIMP-1 mRNA的相对表达量明显低于对照组(P<0.05),但与ox-LDL组比较差异无统计学意义(P>0.05)。结论:AngⅡ可增加人脐动脉平滑肌细胞MMP-9的表达而降低TIMP-1的表达,缬沙坦可以抑制AngⅡ的这种作用。Objective： To study the effect of valsartan on the expression of matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1） in human umbilical artery smooth muscle cell （HUASMC）. Methods： HUASMC was primary cultured, then treated with ox-LDL（ ox-LDL group）, Ang Ⅱ and ox-LDL（Ang Ⅱ group）, Ang Ⅱ, ox-LDL and valsartan （valsartan group）, respectively. In the control group, HUASMC was treated by vehicle. The contents of MMP-9, TIMP-1 in HUASMC supernate fluid were detected by ELISA, and the expression of MMP-9 mRNA, TIMP-1 mRNA were assayed by RT-PCR, then compared them statistically. Results ： MMP-9 was significantly higher in Ang Ⅱ group than those in other groups （ P 〈 0. 01, in each）, TIMP-1 in ox-LDL group and in Ang Ⅱ group were significantly lower than that in control group（P 〈0.01, in each）, TIMP-1 showed no significant difference between valsartan group and control group by ELISA （ P 〉 0. 05 ）. In Ang Ⅱ group, the expression of MMP-9 mRNA was significantly higher than those in other groups（P 〈 0.01, in each） , and the expression of TIMP-1 mRNA was lower than other groups（P 〈0. 01, in each）. The expression of TIMP-1 mRNA in valsartan group was lower than that in control gruop （ P 〈 0.05 ）, but no difference between valsartan group and ox-LDL group （ P 〉 0.05 ）. Conclusion： Ang Ⅱ can induce the secretion of MMP-9 and inhibit the expression of TIMP-1. Valsartan can depress the role of Ang Ⅱ.

关 键 词：缬沙坦 急性冠状动脉综合征 血管紧张素Ⅱ 基质金属蛋白酶-9 组织型金属蛋白酶组织抑制物-1 动脉粥样斑块 

分 类 号：R96[医药卫生—药理学]