不同剂量卡维地洛干预对心肌梗死后心力衰竭大鼠心肌细胞凋亡和凋亡相关基因表达的影响

目的 :探讨不同剂量卡维地洛 (CAR)对心肌梗死 (MI)后大鼠心肌细胞凋亡的影响及CAR治疗充血性心力衰竭 (CHF)的作用机制。方法 :将雄性Waistar大鼠前降支结扎 ,于术后 1周开始分别予大剂量CARHCAR组 ,6 0mg/ (kg·d) ]和小剂量CARLCAR组 ,6mg/ (kg·d) ]干预 7周 ,观察不同剂量CAR对大鼠血流动力学参数、心肌细胞凋亡、Fas、Fas配体 (FasL)和Bcl 2mRNA表达的影响。结果 :CAR可改善心功能指标 ,降低心肌细胞凋亡指数、Fas及FasL的mRNA水平 ,上调Bcl 2表达 ,其中对心肌细胞凋亡指数、Fas及Bcl 2mRNA表达的影响以HCAR组明显。结论 :CAR可有效地减少MI后心肌细胞凋亡 ,防治CHF ,效果以大剂量明显 ,这可能与其对凋亡相关基因表达影响的差异有关

Effects of Carvedilol at different dose on cardiac myocyte apoptosis and apoptosis-associated gene during heart failure subsequent to myocardial infarction in rats

Objective:To study the effects and mechanisms of carvedilol (CAR) at different dose on cardiac myocyte apoptosis during congestive heart failure (CHF) subsequent to myocardial infarction (MI) in rats.Methods:Using a animal model of MI, induced by the left coronary artery ligation in male waistar rats, hemodyanmics parameters, cardiac myocyte apoptosis, the expression of mRNA of Fas, FasL and Bcl 2 were investigated in the untreated experimental group (MI group) at 8 week after operation and treated experimental groups in which rats were treated with CAR at a higher dose (HCAR group, 60 mg.kg -1 .day -1 ,n=10) and at a lower dose (LCAR group, 6 mg.kg -1 .day -1 , n=10) for 7 weeks since 1 week after operation. The sham operated rats served as control (SH group, n=10).Results:Both of CAR at a higher and at a lower dose can improved heart function and decrease apoptosis index in rats with MI. The number of myocytes apoptosis and the level of mRNA of Fas were significantly lower and Bcl 2 was markedly higher in HCAR group than those in LCAR group.Conclusion:CAR can effectively decrease myocardiocyte apoptosis, prevent and cure CHF. The effect is dose dependent, associates with changes of the expression of apoptosis associated gene.