缺血时间对大鼠心肌缺血再灌注损伤及基质金属蛋白酶表达的影响

Impact of ischemia duration on myocardial ischemia-reperfusion injury and MMPs expression

目的观察不同缺血时间对大鼠心肌缺血再灌注损伤的影响并探讨其可能机制。方法雄性SD大鼠24只,采用完全随机法分为心肌缺血30 min后再灌注组(A组,8只),心肌缺血10 min后再灌注组(B组,8只),假手术组(C组,8只)。采用组织病理学检查和超声心动图检测评价3组大鼠心肌损伤、心脏功能及心室重构情况,并采用RT-PCR和Western blot法检测3组大鼠心肌组织基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)、基质金属蛋白酶组织抑制剂1(TIMP-1)的表达。结果与C组比较,A组、B组大鼠心肌损伤后7、14 d LVEF、左心室短轴缩短率明显降低,收缩末室间隔厚度明显减小(P<0.05);A组、B组大鼠心肌组织中MMP-2和MMP-9表达明显增加,TIMP-1表达明显减少,且A组较B组变化更明显(P<0.05)。结论延长缺血时间会促使再灌注心肌MMP-2、MMP-9表达增加,TIMP-1表达减少,继而导致心肌缺血再灌注损伤的加重。

Abstract：Objective To observe the impact of different ischemia durations on myocardial ischemia-reperfusion injury and MMPs expression. Methods Rat models of myocardial ischemia and reperfusion were established with different ischemia durations（group A for 30 minutes, group B for 10 minutes）,and a sham operation group was set as control（group C）. Histopathological examination and echocardiography were used to evaluate the myocardial injury,cardiac function and ventricular remodeling. Reverse transcription PCR and Western blot were used to detect the expression of MMP-2,MMP-9 and TIMP-1 in myocardium. Results Compared with group C, echocardiography indicated that both group A and group B had reduced left ventricular ejection fraction,increased left ventricular end diastolic diameter, reduced end systolic interventrieular septal thickness and decreased left ventricular shortening fraction. Histopathology reveals the rupture of myocardial fibers, fibrous scar tissue regeneration and collagen deposition in both group A and group B. Compared with group C, group A and group B had higher expression of MMP-2 and MMP-9 and lower expression of TIMP-1 in myocardium. All the above changes were much significant in group A than in group B. Conclusion Prolonged ischemia duration would aggravate myocardial isehemia-reperfusion injury by changing expression of MMPs/TIMPs system.