不同剂量卡维地络干预对压力超负荷幼鼠心肌细胞凋亡和凋亡相关基因表达的影响

Effects of carvedilol at different doses on cardiac myocyte apoptosis and apoptosis-associated gene in rats with pressure overload

目的 :探讨不同剂量卡维地络 (CAR)对压力超负荷心肌肥厚幼鼠心肌细胞凋亡的影响 ,以及CAR治疗充血性心力衰竭 (CHF)的作用机制。方法 :建立腹主动脉狭窄所致压力负荷增加心肌肥厚幼鼠模型 ,术后 1周开始给予小剂量CAR(0 .1mg·kg-1·d-1)和大剂量CAR(10mg·kg-1·d-1)干预 7周 ,观察不同剂量CAR对幼鼠血流动力学参数、心肌细胞凋亡、Bcl 2和P5 3蛋白水平表达的影响。结果 :CAR可改善心功能指标 ,降低心肌细胞凋亡指数、上调Bcl 2蛋白及下调P5 3蛋白表达 ,HCAR组作用明显。结论 :CAR可有效减少压力超负荷心肌肥厚幼鼠的心肌细胞凋亡 ,防治CHF ,效果以大剂量明显 。

AIM: To study the effects and mechanism of carvedilol (CAR) at different doses on cardiac myocyte apoptosis in rats with myocardial hypertrophy of CHF. METHODS: Using the animal model of CHF, induced by abdominal aortic constriction in male Wistar rats, hemodyanmics parameters, cardiac myocyte apoptosis, and the expression of Bcl-2 and P53 were investigated in the untreated experimental group (CHF group) at 1 week after operation and treated experimental groups in which rats were treated with CAR at a lower dose (LCAR group, 0.1 mg·kg -1·d -1) and at a higher dose (HCAR group, 10 mg·kg -1·d -1) for 7 weeks since 1 week after operation. The sham-operated rats were as controls (SH group, n=8). RESULTS: Either doses improved heart function and decreased apoptosis index in rats with CHF. The number of myocytes apoptosis and the level of Bcl-2 were significantly higher and P53 was markedly lower in HCAR group than those in LCAR and MCAR groups. CONCLUSION: CAR can effectively decrease myocardiocyte apoptosis, prevent and cure CHF. The effects are dose-dependent, associated with changes of the expression of apoptosis-associated gene.