三磷酸腺苷后处理对兔心肌缺血再灌注损伤保护作用的研究

摘要

目的 观察ATP后处理对再灌注损伤挽救激酶信号通路中的蛋白激酶B(Akt)及细胞外信号调节激酶(ERK1/2)表达的影响,探讨ATP后处理的心血管保护效应及可能机制.方法 选择48只健康新西兰白兔,随机分为缺血再灌注组(再灌注组)、ATP后处理组(后处理组)、磷脂酰肌醇3激酶(PI3K)抑制剂Wortmannin+ ATP后处理组(Wortmannin+ ATP组)、ERK1/2抑制剂PD98059+ ATP后处理组(PD98059+ ATP组),每组12只.建立兔急性心肌缺血再灌注模型.实验终点检测各组心肌梗死面积、细胞凋亡指数,Western blot法检测心肌p-Akt,p-ERK1/2蛋白表达.结果 后处理组心肌梗死面积、细胞凋亡指数明显低于再灌注组(P＜0.01).Western blot检测显示,后处理组p-Akt、p-ERK1/2表达水平明显高于再灌注组(P＜0.05).结论 ATP后处理可以减轻兔缺血再灌注心肌的梗死面积,降低细胞凋亡指数,同时上调p-Akt和p-ERK1/2的表达,提示PI3K/Akt及ERK1/2信号通路参与了ATP后处理对兔缺血再灌注心肌的保护作用.%Objective To study the role of ATP postconditioning in protection of rabbits against myocardial I/R injury and its mechanism by observing its effect on expression of protein kinase P(Akt)and ERK1/2. Methods Forty-eight male New Zealand white rabbits were randomly divided into I/R group, ATP postconditioning group, wortmannin + ATP postconditioning group and PD98059 + ATP postconditioning group(12 in each group). An acute myocardial I/R model was established. Myocardial inarction size and apoptosis index were assayed at the end of experiement. Expressions of myocardial p-Akt and p-ERK1/2 were detected by Western blot. Results The infarction size and apoptosis index were significantly lower in ATP postconditioning group than in I/R group(P<0. 01). Western blot showed that the expression levels of p-Akt and p-ERK1/2 were significantly higher in ATP postconditioning group than in I/R group (P<0. 05). Conclusion ATP postconditioning can reduce the myocardial infarction size and apoptosis index and up-regu-late the expression of p-Akt and p-ERK1/2 in rabbits following I/R injury, indicating that the PI3K/Akt and ERK1/2 signal patheways participate in protecting rabbits against myocardial I/R injury.