阿托伐他汀后处理对GK大鼠心肌缺血再灌注损伤的保护作用
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Protective Effect of Atorvastatin Postconditioning on Myocardial Ischemia-reperfusion Injury in GK Rat
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    摘要:

    目的探讨不同剂量阿托伐他汀后处理对GK大鼠心肌缺血再灌注损伤的作用及其机制。方法将70只GK大鼠随机分为7组(n=10只):假手术组、缺血再灌注组(I/R组)、不同剂量(0.1、0.5、1及2 mg/kg)阿托伐他汀后处理组及阿托伐他汀后处理+LY294002组。TTC染色测定心肌梗死面积,电镜观察心肌细胞超微结构变化及Western blot测定心肌组织磷酸化蛋白激酶B(p-Akt)、总Akt(t-Akt)的蛋白表达。结果阿托伐他汀后处理组心肌梗死面积低于I/R组,心肌线粒体超微结构损伤轻于I/R组,Akt磷酸化水平高于I/R组,其中1 mg/kg和2 mg/kg阿托伐他汀后处理组较显著。PI3K特异性抑制剂LY294002可消除这种作用。结论阿托伐他汀后处理对GK大鼠心肌缺血再灌注损伤有保护作用,这可能与PI3K/Akt通路的激活有关。

    Abstract:

    AimTo investigate the effects of different dosage of atorvastatin postconditioning and its mechanisms on myocardial ischemia-reperfusion injury in GK rat.MethodsSeventy GK rats were randomly divided into seven groups (n=10 each): sham group, ischemia-reperfusion injury (I/R) group, different dosage of atorvastatin (0.1, 0.5, 1 and 2 mg/kg) postconditioning group, atorvastatin+LY294002.Myocardial infarct size (IS), ultrastructural change and myocardial expression of phosphorylated Akt/totalAkt were determined.ResultsMyocardial infarct size and ultrastructural damages were all reduced, myocardial Akt phosphorylation was significantly increased, and Akt was significantly activated in atorvastatin postconditioning group compared with I/R group.The effects were significant at 1 mg/kg and 2 mg/kg atorvastatin postconditioning group, and were significantly attenuated by PI3K inhibitor LY294002.ConclusionAtorvastatin postconditioning could dose-dependently alleviate myocardial ischemia-reperfusion injury in this type 2 diabetic model, which may probably be associated with the increase of the activating PI3K/Akt signaling pathway in the myocardium.

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程振东,吴灵振,郭进建,,赵子文,祝雪丽,蔡平,陈良龙.阿托伐他汀后处理对GK大鼠心肌缺血再灌注损伤的保护作用[J].中国动脉硬化杂志,2012,20(8):709~713.

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  • 收稿日期:2011-11-07
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