Cardioprotective effects of atorvastatin postconditioning on ischemia-reperfusion injury in isolated rat heart:the role of PI3K-Akt, mito-KATP channel and mPTP / 天津医药

ABSTRACT

Objective To observe the postconditioning cardioprotective effects of atorvastatin (ATV) on ischemia-re?perfusion injury in isolated rat heart, and the role of phosphatidylinositol-3-kinase , protein kinase B(PI3K-Akt), mitochon?drial ATP-sensitive potassium (mito-KATP channel) and mitochondrial permeability transition pore (mPTP) thereof. Meth?ods Healthy male Wistar rats were randomly divided into 9 groupsischemia reperfusion (I/R) control group, atorvastatin postconditioning (ATV) group, ATV plus PI3K inhibitor LY294002 (ATV+LY294002) group, LY294002 group, ATV plus mi?to-KATP channel inhibitor 5-hydroxydecanoate (ATV+5-HD) group, 5-HD group, ATV plus mPTP inhibitor ATR (ATV+ATR) group, ATR group and ethanol group. Model rats were given 30-min ischemia followed by 120-min reperfusion. The myocardial infarction size, hemodynamic parameters, creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), nic?otinamide adenine dinucleotide (NAD+) and the expression of myocardial protein kinase B (Akt) and myocardial phospho-pro?tein kinase B (p-Akt) were evaluated. Results Compared with the control group, atorvastatin reduced the myocardial in?farction size, CK-MB and LDH(P<0.05), increased NAD+(P<0.05). There were no significant differences in the myocardi?al infarction size, CK-MB, LDH and NAD+between ATV+LY294002 group, ATV+5-HD group and ATV+ATR group. The hemodynamic parameters were improved in ATV group compared with those in control group. Western blot analysis con? firmed the significant phosphorylation of Akt in ATV group, ATV+5-HD group and ATV+ATR group compared with those of control group. There were no significant differences in the phosphorylation of Akt between ATV +LY294002 group, LY294002 group, ATR group and 5-HD group. Conclusion Atorvastatin postconditioning could attenuate the ischemia-re?perfusion injury through activating the PI3K-Akt, promoting mito-KATP channel opening and inhibiting mPTP opening.