不同剂量卡维地洛对心衰大鼠心肌氧化应激和细胞凋亡的影响  

Effects of carvedilol at different dose on oxidative stress and cardiac myocyte apoptosis in heart failure rats

作　　者：吴强[1] 李隆贵[2] 蔡运昌[1] 杨天和[1] 王晓峰[1] 耿召华[2] 

机构地区：[1]贵州省人民医院心内科,贵州贵阳550002 [2]第三军医大学新桥医院心内科,重庆400037

出　　处：《心脏杂志》2003年第5期410-413,共4页Chinese Heart Journal

基　　金：贵州省科委科学技术基金资助项目 (No.3 0 44 )

摘　　要：目的 :探讨不同剂量卡维地洛 (CAR)对心肌梗死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周开始分别给予大剂量 CAR(HCAR组 ,6 0mg· kg- 1· d- 1 )和小剂量 CAR(L CAR组 ,6 m g· kg- 1· d- 1 )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、心肌丙二醛 (MDA)含量和总抗氧化能力 (TAOC)的影响。结果 :CAR可改善心功能指标 ,降低心肌细胞凋亡指数及 MDA浓度 ,上调 TAOC水平 ,其中对心肌细胞凋亡指数 (HCAR组为 4 .6 %± 1.1% ,L CAR组为 8.0 %± 2 .0 % )、TAOC(HCAR组为 1.92± 0 .2 0 U· mg- 1 ,L CAR组为 1.5 9± 0 .12 U· mg- 1 )的影响以HCAR组明显。结论 :CAR可有效地减少心肌梗死后心肌细胞凋亡 ,防止 CHF的发生、发展 ,效果以大剂量明显 。AIM: To study the effects and mechanisms of carvedilol (CAR) in different doses on cardiac myocyte apoptosis during congestive heart failure (CHF) subsequent to myocardial infarction in rats. METHODS: An animal model of myocardial infarction(MI) was used which was induced by the left coronary artery ligation in male Waistar rats. Twenty-seven rats with MI were divided into three groups, the untreated experimental group ( n =10), the group treated with CAR in a higher dose for seven weeks right after the operation (HCAR group, 60 mg·kg -1·d -1, n =10) and the group treated in a lower dose (LCAR group, 6 mg·kg -1·d -1, n =7). The sham-operated rats served as the control ( n =10). Hemodyanmic parameters, cardiac myocyte apoptosis, the concentration of malondialdehyde (MDA) and total antioxidation capacity (TAOC) were investigated eight weeks after the operation. RESULTS: CAR either in a higher and or in a lower dose improved heart function and decreased apoptosis index and the concentration of MDA, increased the TAOC level in rats with MI. The number of myocytes apoptosis was significantly lower (4.6%±1.1% vs 8.0%±2.0%) and the TAOC level was markedly higher(1.92±0.20 U· mg -1 vs 1.59±0.12 U· mg -1) in the HCAR group than in the LCAR group. CONCLUSION: CAR can effectively decrease cardiomyocyte apoptosis, and can prevent and cure CHF. The effect of CAR is dose-dependent, which may be due to its maintenance of protective antioxidants in myocardium.

关 键 词：卡维地洛 心力衰竭 充血性 细胞凋亡 氧化应激 

分 类 号：Q25[生物学—细胞生物学] Q463