缺血后处理和三磷酸腺苷后处理对心肌缺血再灌注损伤的影响

目的观察缺血后处理(IPO)、ATP和腺苷受体激动剂CGS-21680后处理对心肌缺血再灌注损伤的影响。方法健康新西兰大白兔48只,随机分为对照组、IPO组、ATP组、CGS-21680组,每组12只。测定肌酸激酶同工酶(CK-MB)、丙二醛水平及超氧化物歧化酶(SOD)活力;计算各组兔心肌梗死面积;HE染色观察心肌组织病理形态变化;TUNEL法检测心肌细胞凋亡;实时荧光定量RT-PCR检测心肌组织天冬氨酸特异性半胱氨酸蛋白酶3(caspase-3)mR NA和Bcl-2 mRNA的表达。结果与对照组比较,IPO组、ATP组和CGS21680组血清丙二醛、CK-MB水平及心肌梗死面积明显降低,SOD活力明显升高。IPO组、ATP组和CGS-21680组心肌细胞凋亡指数较对照组明显降低,心肌组织损伤明显减轻。IPO组、ATP组和CGS-21680组较对照组caspase-3 mRNA表达明显下调,Bcl-2 mRNA表达明显上调。结论 IPO与ATP后处理可通过激活腺苷A2a受体,减轻心肌缺血再灌注损伤,其机制可能与上调Bcl-2和下调caspase-3的表达,抑制氧自由基氧化应激损伤,减少细胞凋亡有关。

Effects of ischemia postconditioning and adenosine triphosphate postconditioning on myocardial ischemia-reperfusion injury

Objective To explore the effects and mechanism of ischemic postconditioning(IPO) ,adenosine triphosphate and adenosine receptor agonist postconditioning on myocardial IR injury in rabbits.Methods Forty-eight rabbits were randomly divided into four groups (n = 12 each):IR group,IPO group,ATP group and CGS-21680 group.The levels of CK-MB,MDA and SOD of each group were evaluated at the end of 3h reperfusion.Ischemic and infarct areas were measured by Evans blue and NET staining.Light microscopy was used to observe tissue changes of myocardium. TUNEL method was used to detect apoptotic changes.The expression of caspase-3 and Bcl-2 gene in myocardial tissue was detected by real-time quantitative RT-PCR.Results Compared with IR group,myocardial infarct size,the levels of CK-MB and MDA decreased markedly in IPO group,ATP group and CGS-21680 group,while the level of SOD increased significantly. Compared with IR group,apoptosis indexes were significantly decreased and the histopathological changes of the myocardium were alleviated obviously in IPO group,ATP group and CGS-21680 group.The expression of caspase-3 mRNA was down-regulated,while Bcl-2 mRNA was up-regulated in IPO group,ATP group and CGS-21680 group.Conclusions IPO and ATP postconditioning attenuate myocardial IR injury by activating adensine A2a receptor,the mechanism might be associated with up-regulating the expression of Bcl-2 mRNA and down-regulating the expression of caspase-3 mRNA,inhibiting oxidation stress and decreasing cardiomyocyte apoptosis.