| Objective Previous studys showed that，pharmacological postconditioningcan reduces myocardial ischemia-reperfusion injury. However, there are contradictorydata in the literature regarding the susceptibility of the diabetic heart toischaremia-reperfusion injury and the initiation of cardioprotection by pharma-cological postconditioning. The purpose of this study was to investigate whetherpharmacological postconditioning with atorstatin could reduce diabetic myocardialischemia-reperfusion injury and to probe the potential cardioprotective mechanisms.Methods Seventy GK rats， undergoing40min ischemia and180minreperfusion， were randomly divided into seven groups（n=10each）：（1）Sham，treated with open chest operation but without myocardial ischemia/reperfusion ascontrols;（2）ischemia reperfusion injury(I/R) group, undergoing40min ischemia and180min reperfusion in left anterior descending coronary territory but without otherinterventions;（3-6）different dosage of atorvastatin postconditioning group（0.1,0.5,1or2mg/kg），pushed atorvastatin（0.1,0.5,1or2mg/kg）in external jugular vein slowly3mins before reperfusion;（7） optima dose atorvastatin+LY294002, with anadditional injection of PI3K inhibitor(LY294002)0.3mg/kg in external jugular veinslowly15mins before reperfusion. Myocardial infarct size（IS），ultrastructural changeand myocardial expression of phosphorylated Akt/total AKt，phosphorylated-eNOS/total-eNOS，HSP70were determined, plasma cTnT were also determined.Results Compared with the I/R group,the myocardial infarction size wasdecreased,the lever of cTnT was decreased,the mitochondria injuries was attenuatedin different dosage of atorvastatin postconditioning group（0.1,0.5,1or2mg/kg）.2.Compared with AP0.1mg/kg and AP0.5mg/kg and AP1mg/kg, the AP2mg/kggroup could futher alleviate mitochondria injury, reduce myocardial infarct size， and reduce the lever of cTnT.3. Compared with the I/R group, different dosage ofatorvastatin postconditioning groups （0.1,0.5,1or2mg/kg） could increase theexpression of p-AKt,p-eNOS and HSP70.4. Compared with AP0.1mg/kg andAP0.5mg/kg and AP1mg/kg, the AP2mg/kg group could futher increase theexpression of p-AKt,p-eNOS and HSP70.5.There were no significant differences inthe level of myocardial infarction size、cTnT、mitochondria injuries of myocardialcell，as well as the level of p-AKt,p-eNOS and HSP70between I/R group and LYgroup.Conclusion1.Atorvastatin postconditioning could dose-dependent alleviatemyocardial ischemia-reperfusion injury in this type2diabetic model，which mayprobably be associated with the increase of the activating PI3K-Akt-eNOS signalingpathway in the myocardium.2. Atorvastatin postconditioning attenuates diabetic heartischemia-reperfusion injury in a manner that is reliant on upregulation of HSP70，andHSP70may be a downstream target of PI3K-Akt-eNOS signaling pathway.3.Thediabetic heart may be more susceptible to infarction, however pro survivalmechanisms can still be initiated to provide protection against diabetic heartischaemia-reperfusion injury. |
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