The Relationship Between Calcineurin And Myocardium Apoptosis And Effects Of Carvedilol Intervention

OBJECTIVE To explore the change of calcineurin(CaN) activity and myocardium apoptosis in myocardial ischemia-reperfusion(I/R) injury of rat in vivo,and appraise effects of carvedilol intervention on the myocardial apoptosis and CaN.To approach the relationship between CaN and myocardium apoptosis,and approach the beneficial effects of carvedilol pretreatment and therapy respectively.METHODS Thirty-six male rats were randomly divided into A,B group.A group contain: the sham-operation A group,the I/R A group,the carvedilol pretreatment group,and B group include:the sham-operation B group,the I/R B group,the carvedilol therapy group(n=6 each). Four groups of the sham-operation and the I/R were given Liquor natrii chloridi isotonicus 5 ml·kg^-1·d^-1 through the stomach tube.Two groups of the carvedilol were given carvedilol 20 mg·kg^-1·d^-1.In A groups,the myocardial I/R was induced after 7 d of administration in two groups of carvedilol pretreatment and I/R A by ligation of the left anterior descending branch of the coronary artery(LAD) for 30 min and reperfusion for 3 h.In B groups,the myocardial I/R was induced before 7 d of administration in two groups of carvedilol therapy and I/R B by ligation of LAD for 30 min and reperfusion.When time is up,the myocardial expression of calcineurin was detected with RT-PCR and the rate of the cardiomycyte apoptosis was assessed by flow cytometry.RESULTS The comparison was carried out in groups of A,B group respectively.The mRNA level of CaN and the rate of myocardial apoptosis after I/R both increased in group A and group B.Compared with I/R A group,the mRNA level of CaN in carvedilol pretreatment group degraded(0.704±0.025 vs 0.909±0.016,P＜0.05),as well as the myocardial apoptosis rate (5.5%±0.9%vs 17.3%±1.0%,P＜0.05).The mRNA level of CaN of carvedilol therapy group was more lower than I/R B group(0.631±0.014 vs 0.936±0.025,P＜0.05),as well as the myocardial apoptosis rate(7.6%±1.6%vs19.8%±1.8%,P＜0.05).CONCLUSION The expression of CaN upgraded in myocardial I/R of rats in vivo,as well as the myocardial apoptosis rate.CaN was suggested to own positive effect on the cardiac myocytes apoptosis during I/R.Both intervention of carvedilol pretreatment and therapy was helpful on I/R myocardium,in which carvedilol diminished CaN expression and the cardiomycyte apoptosis.The myocardial protective effect of carvedilol can implement through the abaissement of CaN expression.