基质金属蛋白酶-2对鼠心肌缺血再灌注间质损伤的影响  

The effect of matrix metalloproteinase-2 on interstitium of rat myocardium with ischemic reperfusion

作　　者：韩珂[1] 杨辰垣[1] 肖诗亮[1] 刘成硅[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院心外科,武汉市430022

出　　处：《实用医学杂志》2005年第5期452-455,共4页The Journal of Practical Medicine

摘　　要：目的:探讨基质金属蛋白酶-2(MMP-2)在鼠缺血再灌注心肌的表达,及其与心肌间质损伤和心功能变化的关系。方法:Sprague-Dawley(SD)大鼠24只,随机分为对照组、缺血再灌注组和强力霉素组,每组8只。分别建立改良的Langendorrf离体心灌注模型,测定左室收缩峰压及压力微分,氯胺T法测定胶原含量,免疫组化法测定Ⅰ/Ⅲ胶原比例,酶谱法测定冠脉回流液不同时间点的MMP-2及其酶原(pro-MMP-2)。Westernblot检测心肌MMP-2的表达。结果:MMP-2活性在心肌缺血再灌注早期即明显升高,且其活性与心功能的恢复呈明显的相关性。心肌胶原含量和Ⅰ/Ⅲ比值较对照组均明显下降。强力霉素组表现出明显的保护作用。结论:MMP-2在心肌缺血再灌注间质损伤中起关键作用,应用MMP-2抑制剂可能成为保护心肌缺血再灌注损伤的新方法。Objective To assess the expression of matrix metalloproteinase on rat myocardium with ischemic reperfusion(I/R) and effect on mechanical function recovery of heart and relationship between its expression and interstitium injury. Methods Twenty four SD rats were randomly divided into three groups, control group, ischemic reperfusion group and doxycyline group. Each group includes 8 rats. To establish isolated rat heart modified Langendorrf model retrograde perfusion. The left ventricular peak systolic pressure and its derivate (±dp/dt) were observed. The activity of MMP 2 and pro MMP 2 of coronary effluent on different time were measured by zymography and callgen amount by the method of chloramines T, the ratio of Ⅰ/Ⅲcollagen was assessed by immunohistochemical stain.Results The release of MMP 2 from the heart into coronary effluent was immediately increased as a consequence of ischemic reperfusion, and there was a remarkable correlation between relative activity of MMP 2 and cardiac function recovery. The collagen amount and Ⅰ/Ⅲcollagen ratio decreased subsequently. Doxycycline had protect effect on cardiac interstitium injury with I/R. Conclusion Acute release of MMP 2 during reperfusion after ischimia contributes to cardial mechanic dysfunction. The inhibition of MMPs may be a novel pharmacological strategy for treatment of I/R injury.

关 键 词：基质金属蛋白酶-2(MMP-2) 心肌缺血再灌注 间质 损伤 对照组 强力霉素 心功能 关键作用 结论 比例 

分 类 号：R541[医药卫生—心血管疾病]