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作 者:程振东[1,2] 吴灵振[1,2] 郭进建[1,2,3] 赵子文[1,2] 祝雪丽[3] 蔡平[1,2] 陈良龙[1,2]
机构地区:[1]福建医科大学协和临床医学院心血管内科 [2]福建省冠心病研究所 [3]福建省人民医院心血管内科,福建省福州市350001
出 处:《中国动脉硬化杂志》2012年第8期709-713,共5页Chinese Journal of Arteriosclerosis
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。Aim To investigate the effects of different dosage of atorvastatin postconditioning and its mechanisms on myocardial ischemia-reperfusion injury in GK rat. Methods Seventy 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 pbosphorylated Akt/totalAkt were determined. Results Myocardial infarct size and uhrastruc- tural damages were all reduced, myocardial Akt phosphorylation was significantly increased, and Akt was significantly activa- ted in atorvastatin postconditioning group compared with I/R group. The effects were significant at 1 mg/kg and 2 mg/kg atorvastatin posteonditioning group, and were significantly attenuated by PI3K inhibitor LY294002. Conclusion Atorv- astatin 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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