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 arrhythmia 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 cardiomyoeyte 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.
出处
《国际心血管病杂志》
2011年第4期245-248,共4页
International Journal of Cardiovascular Disease
关键词
环孢素
心肌缺血-再灌注损伤
线粒体通透性
CyclosporineA
Myocardial ischemia-reperfusion injury
Mitochondrial permeability
