PEP-1超氧化物歧化酶融合蛋白对大鼠心肌缺血再灌注细胞凋亡的影响

Effects of PEP-1-superoxide dismutase fusion protein on cardiomyocyte apoptosis in rat myocardium after ischemia-reperfusion

目的探讨PEP-1超氧化物歧化酶(SOD1)融合蛋白对大鼠心肌缺血再灌注细胞凋亡指数、Bax和Bcl-2蛋白表达的影响。方法 SD大鼠40只,制作心肌缺血再灌注模型,分为假手术组、缺血再灌注组、PEP-1-SOD1 100、300和500 μg组,每组8只。TUNEL法及免疫组织化学法检测心肌细胞凋亡指数(AI)及Bax、Bcl-2蛋白的表达。结果假手术组AI、Bax及Bcl-2蛋白表达水平均较低。PEP-1-SOD1各组AI和Bax蛋白的表达较缺血再灌注组明显降低,Bcl-2蛋白的表达明显增加,Bax/Rcl-2比值明显下降(P<0.05,P<0.01)。结论 PEP-1-SOD1可抑制缺血再灌注心肌细胞凋亡,原因可能为其减轻氧化应激、下调Bax和上调Bcl-2蛋白表达水平。

Objective To explore the influence of PEP-1 SOD1 fusion protein on cardiomyocyte apoptosis, expression of Bax and Bcl-2 proteins following myocardial ischemia-reperfusion in rats. Methods Forty rats were randomly divided into sham-operated group, ischemia-reperfusion group,PEP 1-SOD1 100,300 and 500 pig groups（8 rats in each group）. Ischemia-reperfusion model was established by left anterior descending coronary artery ligation for 1 h, followed by 2 h of reperfusion. Cardiomyocyte apoptotic index（AI）,Bax and Bcl-2 in cardiomyocytes were detected with TUNEL and immunohistochemistry methods, respectively. Results The levels of AI, Bax and Bcl-2 proteins were low in sham-operated group. In PEP-1-SOD1 groups,the levels of AI,Bax and Bax/Bcl-2 ratio were decreased significantly as compared with ischemia-reperfusion group. However, the level 0. 01）. Conclusion of Bcl-2 protein was up-regulated in PEP-1-SOD1 groups （P 〈 0.05,P〈0.01）.Conclusion PEP-1-SOD1 can inhibit the cardiomyocyte apoptosis probably through the mechanisms of alleviating oxidative stress, down regulating Bax and up-regulating Bcl-2 proteins.