环孢素预处理对大鼠心肌缺血-再灌注损伤的保护作用

摘要

目的:研究环孢素(CsA)预处理对大鼠心肌缺血-再灌注损伤的保护作用,并探讨其可能机制.方法:36只10周龄SD大鼠随机分为环孢素预处理(CsA)组、缺血-再灌注(IR)组、假手术(Sham)组,每组12只.应用Medlab生物信号采集处理系统连续监测各组左心室收缩末期压(LVESP)和心电图.再灌注结束后采集血液、心肌组织标本,检测血清肌酸激酶(CK-MB)、乳酸脱氢酶(LDH)、肿瘤坏死因子-α(TNF-α)水平及心肌组织半胱氨酸蛋白酶-3(Caspase-3)活性、心肌细胞线粒体通透性.结果:与IR组比较,CsA组大鼠再灌注性心律失常明显减少,抬高的ST段回落明显,LVESP保持稳定;血清CK-MB、LDH、TNF-α浓度明显降低;心肌组织Caspase-3活性显著降低;心肌细胞线粒体通透性减小.结论:CsA预处理能够减轻大鼠心肌缺血-再灌注损伤,其机制可能与CsA减小心肌细胞线粒体通透性,改善线粒体功能障碍;减少TNF-α的生成,减轻炎症反应和损伤;下调心肌组织Caspase-3表达,减少心肌细胞凋亡等有关.%Objective: The purpose of this study was to investigate the protective effects of cyclosporineA(CsA) on myocardial ischemia-reperfusion injury in rats and its possible mechanism.Methods:Thirty-six ten-week old Sprague-Dawley (SD) rats were randomly assigned to 3 groups:namely, cyclosporineA pretreating (CsA) group, ischemia-reperfusion (IR) group and sham operation (Sham) group. Each group consisted of 12 rats. (1) CsA group: myocardial ischemia and reperfusion model after a week of CsA gavage (45 minutes ischemia and 6 hours reperfusion of anterior descending coronary) (2) IR group: myocardial ischemia and reperfusion model after a week of equal amount of physiological saline gavage (3) Sham group. ECG and left ventricular end-systolic pressure ( LVESP )were monitored continually by Medlab. The blood and myocardial tissue samples were taken after reperfusion. CK-MB, LDH, and TNF-α in serum, Caspase-3 in myocardial tissue and cardiomyocyte mitochondrial permeability were detected after the experiment. Results: In comparison with IR group,reperfusion arrhythrnia in the rats in CsA group was reduced significantly within reperfusion; Raised ST segments were progressively decreased to considerable extent, while LVESP was normally stable; CK-MB,LDH and TNF-α in serum decreased significantly; the Caspase-3 activity in myocardial tissue was significantly lower and cardiomyocyte mitochondrial permeability decreased. Conclusion: These results suggested that myocardial ischemia-reperfusion injury can be relieved through CsA pretreatment. Its mechanism may be relate to reducing cardiomyocyte mitochondrial permeability, andimproved mitochondrial function improved; down -regulating expression of TNF-α so as to reduce inflammatory response and inflammatory injury; decreasing myocardial tissue expression of Caspase-3 to reduce cardiac cell apoptosis.