卡维地洛预处理对缺血再灌注心肌钙调磷酸酶和心肌凋亡的影响

Beneficial effects of carvedilol pretreatment on calcineurin and myocardium apoptosis in models of acute myocardial ischemia and reperfusion

目的研究卡维地洛预处理对大鼠在体心肌缺血再灌注(I/R)后钙调磷酸酶(CaN)水平和细胞凋亡率的影响,探讨卡维地洛心肌保护作用的机制。方法Wistar雄性大鼠24只,随机分为4组(均n=6):伪手术组、L/R组、卡维地洛A组及卡维地洛B组,前2组大鼠灌胃给予生理盐水5mL·kg^(-1)·d^(-1),卡维地洛A组和B组则分别给予卡维地洛20、60mg·kg^(-1)·d^(-1)。7d后建立大鼠在体心肌I/R模型,I/R组及卡维地洛A、B组结扎左冠状动脉前降支30min复灌3h,伪手术组仅穿线,不结扎。RT-PCR法检测心肌CaNmRNA的表达水平,流式细胞术检测心肌细胞凋亡率。结果I/R后CaNmRNA的表达水平上升,心肌细胞凋亡率增加。卡维地洛可降低I/R心肌CaNmRNA的表达水平及心肌细胞凋亡率,以60mg·kg^(-1)·d^(-1)组更为明显(均P<0.05)。结论预防性使用卡维地洛对大鼠I/R心肌具有明显的保护作用,使CaNmRNA表达及心肌细胞凋亡率均降低。

AIM To approach the effects ofcarvedilol pretreatment on calcineurin （CAN） and myocardium apoptosis in a rat model of acute myocardial ischemia-reperfusion （I/R） injury. METHODS Twenty-four male rats were randomized into four groups （n = 6 in each group） and respectively administered with liquor natrii chloridi isotonicus 5 mL· kg^-1·d^-1 （sham-operation group and ischemia-reperfusion group）, carvedilol 20 mg·kg^-1· d^-1 （carvedilol A group） and carvedilol 60 mg· kg^-1· d^-1 （carvedilol B group） for 7 consecutive days, Then the myocardial ischemia-reperfusion was induced in carvedilol A group, carvedilol B group and ischemia-reperfusion group by ligation of the left anterior descending branch of the coronary artery for 30 min and reperfusion for 180 min. The myocardial expression of CaN was detected with RT-PCR and the rate of the cardiomycyte apoptosis was assessed by flow cytometry. RESULTS Both the mRNA level of CaN and the rate of myocardial apoptosis increased after I/R. Compared with I/R group, the mRNA level of CaN and myocardial apoptosis rate decreased significantly in both carvedilol groups （P 〈 0.05） , especially in carvedilol B group. CONCLUSION Carvedilol has positive effect on the cardiac myocytes apoptosis. The pretreatment of carvedilol is helpful in I/R myocardium through diminishing CaN activity.