大鼠缺血再灌注心肌基质金属蛋白酶不同时程的表达

Time-dependent changes of matrix metal proteinases after myocardial ischemia-reperfusion injury in rats

目的:探讨大鼠心肌缺血再灌注不同时间点基质金属蛋白酶(MMP)-1,2,9的表达及其意义。方法:建立大鼠在体心肌缺血再灌注损伤模型,采用免疫组化法检测心肌组织中MMP-1,2,9的表达,以四通道电生理仪检测心功能,比色法测定血浆肌酸激酶(CK)、乳酸脱氢酶(LDH)和髓过氧化物酶(MPO)活性。结果:与假手术组相比缺血再灌注组心功能明显降低,CK、LDH和MPO活性显著增高,呈明显的时间依赖性,于再灌注2 h达到峰值(P<0.01)。缺血再灌注后大鼠心肌中MMP-1的表达水平明显高于假手术组和缺血组(P<0.05),以再灌注1 h最为明显(P<0.01),且与心功能的改变呈负相关(r=-0.503^-0.748,P均<0.01);MMP-2没有表达;MMP-9的表达于再灌注1 h开始增强,再灌注2 h达到高峰(P<0.01),与心功能呈负相关(r=-0.732^-0.855,P均<0.01)。结论:MMPs可能参与心肌缺血再灌注损伤过程。

Objective： To investigate the changes and significance of MMP-1, 2, 9 in myocardium of rats during myocardial ischemia-reperfusion （I/R）. Methods： The models of I/R were successfully established in anaesthetized rats. Immunohistochemical SABC method .and.computerized image analysis were used to observe alterations of MMP- 1, 2, 9 protein in myocardium of rats. The function of left ventricle was measured by instrument of collecting physiological signals. The activities of CK, LDH , MPO were assayed by colorimetry method. Results： There were obviously deterioration in the left ventricular function and the activities of CK, LDH and MPO increased （P〈0.01 all） after ischemia-reperfusion; those changes were time-dependent. The expression of MMP- 1, 9 were significantly enhanced after ischemia-reperfusion （P〈0.05） and reached peak at the first h, second h of reperfusion in myocardium of rats respectively （P〈0.01 all）. The expression of MMP-1, 9 were negatively correlated with the changes of heart function during myocardial ischemia-reperfusion （r=- 0. 503 - - 0. 855, P〈0. 01 all）. The MMP-2 could not be detected by immunohistochemistry with the anti-MMP-2 antibody. Conclusion.. MMPs may play a key roles in myocardial ischemia-reperfusion injury.