Olprinone Allevintes Myocardial Ischemia/reperfusion Injury Via Regulating Autophagy In Rats

Objective:To observe the effects of olprinone on ischemia/reperfusion(I/R)induced myocardial injury in male(Sprague-Dawley,SD)and explore its mechanisms.Method:Rats were subjected to a 30-min coronary arterial occlusion followed by 24 hours reperfusion.The survival rats were randomly divided into sham group(sham group,n=6),ischemia reperfusion group(I/R group,n=9),ischemia reperfusion+low dose of olprinone group(IR+olprinone-L group,n=6),ischemia reperfusion+medium dose of olprinone group((IR+olprinone-M group,n=6),ischemia reperfusion+high dose of olprinone group((IR+olprinone-H group,n=6).A MAP heart function analysis system was used to measure hemodynamic parameters;TTC staining method was used to detect the myocardial infarct size;24-hour mortality of SD rats was recorded;western blot was used to detect the expressions of Caspase-3,Bax,Bcl-2,LC3B/LC3A,Beclin-1.Results:Cardiac function in I/R group was lower than that in sham group,which was significantly improved by being pretreated with olprinone(P<0.01),but SAP?DAP?MAP?Pmean had no significant difference(P>0.05).The percentage of myocardial infarct size inolprinone-M and olprinone-H group was lower than that in I/R group(P<0.05).There was no significant difference in mortality between each group within 24 hours.Compared with sham group,the expression of Caspase-3 and Bax was obviously up-regulated in I/R group(P<0.01),whereascaspase-3 was down-regulated in olprinone-M group(P<0.05)and Bax wasinhibited by different doses of olprinone(P<0.05),but the expression of Bcl-2 increased(P<0.05);furthermore,the ratio of Bcl-2/Bax decreased in I/R group(P<0.01)andincreased with different degrees in different doses of olprinone(P<0.05).Meanwhile,compared with sham group,the expression of Beclin-1 wasup-regulated in I/R group(P<0.05),and also increasedin olprinone-L and olprinone-M group(P<0.05),but the ratio of Bcl-2/Beclin-1 decreased in different doses of olprinone with sinificant difference in olprinone-M group(P<0.05);moreover,different doses of olprinone elevated the ratio of LC3B/LC3A(P<0.05),with the ratio in olprinone-M group in middle.Conclusion:olprinone can strengthen the cardiac function of myocardial ischemia/reperfusion injury,without leading to disorders in hemodynamics;by regulating autophagy with anti-apoptotic protein,olprinone can make autophagy reach to an appropriate level,usingthe mechanism of autophagy to preventing the myocardium from injury.