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.
出处
《中国动脉硬化杂志》
CAS
CSCD
北大核心
2012年第8期709-713,共5页
Chinese Journal of Arteriosclerosis
