蛋白酶体抑制剂MG-132对大鼠急性心肌缺血再灌注损伤的保护作用研究

目的：研究蛋白酶体抑制剂MC-132对大鼠急性心肌缺血再灌注损伤的影响。方法：结扎SD大鼠左冠状动脉前降支30min后，松开结扎线再灌注6h制作心肌缺血再灌注模型。治疗（I30minR/6h＋T）组于再灌注前5min静脉注射蛋白酶体抑制剂MG-1320．75mg／kg，对照（（I30minR/6）组、假手术（Sham）组和缺血30min无再灌注（I30min）组注射与之相同容积的生理盐水，观察各组心肌梗死体积、心肌酶标志物水平变化。结果：与Sham组相比，I30min组的心肌梗死体积以及心肌梗死体积占左室心肌体积的百分比均明显增加（P〈0．01），血浆肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、肌钙蛋白Ⅰ（TnⅠ）显著升高；再灌注前蛋白酶体抑制MG-132治疗则明显减小了缺血30min再灌注6h组大鼠的心肌梗死体积（P〈0．05）以及降低了血浆心肌损伤标志物水平（P〈0．05）。结论：MG-132能有效地预防急性心肌梗死后的再灌注损伤。

Protective effect of proteasome inhibitor MG-132 on myocardial reperfusion injury in rats

Objective: To investigate the effect of proteasome inhibitor MG-132 on myocardial infarction size and biochemical marker levels in rat myocardium after reperfusion injury.Methods: Adult Sprague-Dawley rats were randomly divided into 4 groups: left anterior descending(LAD) coronary artery ligation for 30 minutes without treatment(I30min),LAD ligation for 30 minutes with subsequent 6 hours reperfusion without treatment(I30min/R6h),LAD ligation for 30 minutes with subsequent 6 hours reperfusion with treatment(I30min/R6h+I30min/R6h) and Sham(Sham30min).After LAD was ligated for 25 min,at 5 min before reperfusion,MG-132(0.75mg/kg)or sterile saline was given to all the treatment group/sham rats,the myocardial infarct size,levels of serum creatine kinases(CK),CK muscle-brain fraction(CK-MB),and troponin I(TnI),were measured.Results: Compared with Sham group,the myocardial infarct size and the ratio of the volume of myocardial infarct over the total volume of left ventricular wall,as well as the levels of serum CK,CK-MB,TnI were significantly increased in I30mingroup(P<0.01).While proteasome inhibitor-MG-132 treatment significantly reduced the size of myocardial infarct and decreased serum CK,CK-MB,TnI levels in I30min/R6h+T group(P<0.05).Conclusion: Our data suggest that myocardial reperfusion injury can be inhibited by proteasome inhibitor MG-132.