Pharmacological Postconditioning With Rosuvastatin Attenuates Myocardial Ischemia-reperfusion Injury In Rat

Objective: Myocardial ischemia postconditioning can attenuate myocardial ischemina-reperfusion injury dramaticly. A lot of pharmacological agents which target PI3K/ Akt/ eNOS pathway, to be used at the time of myocardial reperfusion, could induce a pharmacological postconditioning. The current study was conducted to investigate whether rosuvastatin could induce a pharmacological postconditioning and to investigate the potential cardioprotective mechanisms in rat.Methods: The in vivo rat model of myocardial ischemia-reperfusion injury was established by coronary artery ligature. Rats were randomly divided into 4 groups(n=12):â‘ Ischemia-reperfusion injury group(IR), 0.9% NaCl 1ml/kg was given intravenously 3 minutes before starting the reperfusion after temporary coronary artery occlusion for 30minutes in anaesthetized rats.â‘¡Rosuvastatin postconditioning group(Statin), rosuvastatin 10mg/kg was given intravenously 3 minutes before reperfusion.â‘¢Rosuvastatin+wortmannin group(Statin+W), The PI3K inhibitor wortmannin 15ug/kg was given intravenously 15 minutes before reperfusion; Rosuvastatin 10mg/kg was given intravenously 3 minutes before reperfusion.â‘£Rosuvastatin+ L-NAME group(Statin+L), the NOS inhibitor L-NAME 15 mg/kg was given intravenously 15 minutes before reperfusion; Rosuvastatin 10mg/kg was given intravenously 3 minutes before reperfusion. After 120 minutes reperfusion, rats were executed, plasma CK-MB and LDH were measured,myocardial infarct size was determined by Evans blue and TTC staining, myocardial ultrastructure was detected by electro-microscopic visualization,and the activity of the PI3K signaling cascade was determined by Western blot analysis.Results:â‘ Compared with the IR group,the level of CK-MB and LDH were decreased,the myocardial infarction size was diminished, and ultrastructure injury of myocardial cell was attenuated significantly, while the level of phospho-Akt(Ser473) and phospho-eNOS ( Ser1177 ) was increased significantly in Statin group(P<0.05).â‘¡There were no significant differences in the level of CK-MB,LDH, myocardial infarction size, ultrastructure injury of myocardial cell, as well as the level of phospho-Akt(Ser473)and phospho-eNOS(Ser1177)between IR group and Statin+W group(P>0.05).â‘¢Although the level of phospho-Akt(Ser473)and phospho-eNOS(Ser1177)were increased significantly(P<0.05)in Statin+L group,there were no significant differences in the level of CK-MB,LDH, myocardial infarction size, and ultrastructure injury of myocardial cell between IR group and Statin+L group(P>0.05).Conclusions:â‘ Rosuvastatin can induce a pharmacological postconditioning by avtivating the PI3K/ Akt/eNOS pathway.â‘¡Pharmacological postconditioning with rosuvastatin can attenuate myocardial ischemia-reperfusion injury in rat.â‘¢Pharmacological postconditioning with rosuvastatin attenuates myocardial ischemia-reperfusion injury in an NO-dependent manner.â‘£Pharmacological postconditioning with rosuvastatin may be recommended in the reperfusion therapy of acute myocardial infarction in patients.