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《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2003年第5期

页码:

410-413

栏目:

实验研究

出版日期:

2003-09-01

文章信息/Info

Title:

Effects of carvedilol at different dose on oxidative stress and cardiac myocyte apoptosis inheart 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

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

Author(s):

WU Qiang¹;  LI Long-gui²;  CAI Yun-chang¹;  YANG Tian-he¹;  WANG Xiao-feng¹;  GENG Zhao-hua²

1.Department of Cardiology, People’s Hospital of Guizhou Province, Guiyang, Guizhou 550002, China; 2.Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China

关键词:

卡维地洛; 心力衰竭; 充血性; 细胞凋亡; 氧化应激

Keywords:

Carvedilol;  congestive heart failure;  apoptosis;  oxidative stress

分类号:

Q25;Q463

DOI:

-

文献标识码:

A

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, 60mg·kg- 1·d- 1)和小剂量CAR(LCAR 组, 6 mg·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% ,LCAR组为8.0%±2.0%)、TAOC (HCAR 组为1.92±0.20 U · mg- 1, LCAR 组为1.59±0. 12U · 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,这可能与其维护心肌抗氧化防御系统有关。

Abstract:

AIM: To study the effects and mechanisms of carvedilol (CAR) in different doses on cardiac myocyte apoptosis du ring 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 m g·kg- 1·d- 1, n= 10) and the group treated in a lower dose (LCAR group, 6m g·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 M I. 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·m g- 1 vs 1.59±0.12 U ·m g- 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 main tenance of protective antioxidants in myocardium.

参考文献/References

[1] Givertz MM, Sawyer DB, Colicci WS, et al. A ntioxidants and myocardial contractility illuminating the“dark side ”of B-adrenergic receptor activation [J] . Circulation, 2001, 103(6):782-783.

[2] Sawyer DB, Colicci WS. Mitochondrial oxidative stress in heart failure: “oxygen wastage”revisited [J]. Circ R es, 2000, 86(2):119-120.

[3] Cesselli D, Jakoniuk I, Barlucchi L, et al. Oxidative stress-mediated cardiac cell death is a major determinant of ventricular dysfunction and failure in dog dilated cardiomyopathy [J] . Circ Res, 2001, 89(3):198-200.

[4] Ma XL, Kumar S, Gao F, et al. Inhibition of p38 mitogen-activated protein kinase decrease cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion [J] . Circulation, 1999, 99(13):1685-1691.

[5] Eichhorn EJ, Bristow MR. The carvedilol prospective randomized cumulative survival(COPERNICUS) trial [J]. Curr Control T rials Cardiovasc Med, 2001, 2(1):20-23.

[6] Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial [J] . Lancet, 2001, 357(9266):1385- 1390.

[7] Abreu RM, Santos DJ, Moreno AJ, et al. Effects of Carvedilol and its analog BM 2910228 on mitochondrial function and oxidative stress [J]. J Pharmacol Exp Ther, 2000, 295(3):1022-1030.

备注/Memo

备注/Memo:

收稿日期：2002-06-24.

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更新日期/Last Update: 2003-09-01