缺血预处理减轻肥厚心肌缺血再灌注损伤及其信号途径

Ischemia preconditioning attenuates ischemia-reperfusion injury in isolated hypertrophied rat heart and the involved signaling pathway

目的探讨缺血预处理(IPC)对肥厚心肌体外缺血再灌注(IR)损伤的影响及其信号机制。方法48只心肌肥厚大鼠随机分为4组:IR对照组I、PC组I、PC加磷脂酰肌醇-3激酶(PI3K)抑制剂Wortmannin处理组、Wortmannin处理对照组,观察IPC对心肌肥厚大鼠体外IR心脏左心室收缩压、冠状动脉流量、肌酸磷酸激酶(CPK)和乳酸脱氢酶(LDH)释放、心肌梗死范围以及心肌蛋白激酶B(Akt)、糖原合成酶激酶-3β(GSK-3β)磷酸化的影响。结果与IR对照组比较,IPC组心脏左心室收缩压、冠状动脉流量显著提高,CPK、LDH释放减少,心肌梗死范围减小,心肌Akt、GSK-3β磷酸化水平增高,Wortmannin能够抑制IPC所致的Akt、GSK-3β磷酸化,但只能部分消除IPC的心脏保护效应。结论IPC能够减轻心肌肥厚大鼠体外心脏IR损伤,PI3K、Akt、GSK-3β信号途径参与介导IPC对体外IR肥厚心肌的保护作用。

Objectives To explore the effects of ischemia preconditioning on ischemia-reperfusion injury in isolated hypertrophied rat heart and investigate the signal mechanism underlying the role of ischemia preconditioning.Methods Forty-eight cardiac hypertrophied rats were randomly divided into 4 groups： ischemia reperfusion （IR） control group, IR treated with ischemia preconditioning （IPC） group, IR treated with IPC and phosphatidylinositol-3-kinase （PI3K） inhibitor Wortmannin group, and IR treated with Wortmannin alone group. The effects of ischemia preconditioning on left ventricular systole pressttre（LVSP）, coronary artery flow, creatine phosphokinase （CPK） and lactate dehydrogenase （LDH） release, myocardial infarction size, and the level of myocardial phospho-protein kinase B（ p-Akt）, phospho-glycogen synthase kinase-3β（p-GSK-3β） were evaluated. Results LVSP and coronary artery flow were improved significantly, and the release of CPK and LDH was reduced significantly with significant reduction of myocardial infarction size in IPC group as compared with IR control group. Meanwhile, the levels of p-Akt and p-GSK-3β were increased in IPC group compared with those in IR control group. PI3K inhibitor Wortmannin inhibited the phosphorylation of Akt and GSK-3β induced by ischemia preconditioning, but only abolished partly the cardioprotective effect of ischemia preconditioning. Conclusion Ischemia preconditioning attenuates ischemia-reperfusion injury of isolated hypertrophied rat heart. The PI3K-Akt-GSK-3β signaling pathway is involved in mediating cardioprotection of ischemia preconditioning.