摘要
目的 从细胞内钙调节和细胞凋亡角度探讨卡维地洛治疗心力衰竭的机制。方法 采用结扎冠状动脉复制心力衰竭大鼠模型 ,对照观察非选择性 β 受体阻滞剂卡维地洛和α1 受体阻滞剂特拉唑嗪干预心衰对左室心肌细胞凋亡率和肌浆网钙泵 (SERCA2a)活性的影响。结果 与对照组 (C组 )相比 ,心衰组 (F组 )SERCA2a活性显著降低 (P <0 .0 1) ,心肌细胞凋亡率显著升高 (P <0 .0 1) ;特拉唑嗪组 (T组 )心肌细胞凋亡率、SERCA2a活性与F组无显著差异 (P >0 .0 5 ) ;卡维地洛剂量依赖地降低心肌细胞凋亡率 ,增高SERCA2a活性。SERCA2a活性与心肌细胞凋亡率显著负相关 (r =-0 .814 ,P <0 .0 0 1) ,与 +dp/dtmax、-dp/dtmax显著正相关 (r =0 .691、0 .64 5 ,P <0 .0 0 1)。结论 SERCA2a活性异常 ,可能参与心力衰竭心肌细胞凋亡的调节。增加SERCA2a活性 ,抑制心肌细胞凋亡 ,可能是卡维地洛治疗心力衰竭的重要机制。卡维地洛的上述效应与α1 受体阻滞作用无关。
Objective To study the mechanism of carvedilol therapy of congestive heart failure. Methods After chronic heart failure model was established by ligation of the left coronary artery in rats, rats were treated with carvedilol and terazosin. Then hemodynamic parameters, activity of sarcoplasmic reticulum(SR) Ca 2+ pump(SERCA 2a ) and the rate of cardiomyocyte apoptosis were determined. Results Compared with those of the control group( group C), the activity of SR Ca 2+ pump in the heart failure group(group F) decreased( P <0.01) but the rate of cardiomyocyte apoptosis increased significantly( P <0.01). There was no significant difference between terazosin treated group(group T) and group F( P >0.05). Carvedilol intervention reduced the rate of cardiomyocyte apoptosis, but enhanced the activity of SR Ca 2+ pump significantly in dose dependent manner. The activity of SR Ca 2+ pump was negatively correlated with the rate of cardiomyocyte apoptosis( r =-0.814, P <0.001) but positively with +dp/dt max and -dp/dt max ( r =0.691, 0.645, respectively, P <0.01). Conclusion Abnormality of SERCA 2a activity may contribute to the regulation of cardiomyocyte apoptosis in the progress of heart failure. The inhibition of myocyte apoptosis and enhanced activity of SERCA 2a may be effective mechanisms of carvedilol in the treatment of congestive heart failure. The beneficial effects of carvedilol on SERCA 2a activity and cardiomycyte apoptosis are not related to the blocking effect of α 1 adrenergic receptor.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2003年第9期770-773,共4页
Journal of Third Military Medical University
关键词
心力衰竭
肌浆网钙泵
凋亡
P-受体阻滞剂
congestive heart failure
sarcoplasmic reticulum Ca 2+ pump
apoptosis
β blocker