卡维地洛对多柔比星诱导心肌病大鼠氧化应激的影响

Influence of carvedilol on oxidative stress in rat with adriamycin-induced cardiomyopathy

目的:探讨卡维地洛(carvedilol,CVD)对多柔比星(adriamycin,ADR)致心肌病大鼠氧化应激水平的影响及其可能机制。方法:采用腹腔注射多柔比星建立心肌病大鼠模型,随机分为卡维地洛组和多柔比星组,每组10只。另取正常大鼠10只为正常对照组。卡维地洛组每日给予卡维地洛60 mg/kg;多柔比星组、正常对照组每日给予相同体积生理盐水,观察8周。第9周行心脏超声和血流动力学检测,测定心室胶原含量,总抗氧化能力和丙二醛浓度。结果:卡维地洛组与多柔比星组相比,可显著提高左室射血分数(P<0.01);降低心肌胶原容积分数(P<0.01)。与正常对照组相比,多柔比星组总抗氧化能力显著降低(P<0.01),丙二醛浓度显著升高(P<0.01);而与多柔比星组相比,卡维地洛组可显著提升总抗氧化能力(P<0.01),明显降低丙二醛浓度(P<0.05)。结论:卡维地洛能显著改善多柔比星引起的血流动力异常,改善心脏收缩与舒张功能,逆转心肌重塑,可能与其提高心肌抗氧化应激能力有关。

Objective： To investigate the influence of oxygen stress in rat with adriamycin-induced cardiomyopathy, and to intervene with the third-generation blocker： carvedilol to explore its possible mechanism. Methods： Male Sprague-Dawley rats were administered adriamycin intraperitoneally injected. Randomly divided into two groups （ n = 10 in each group） ： carvedilol group （ 60 mg/kg daily）, adriamycin group and another normal heart control group（giving an equivalent volume of 0.9% saline daily）. After 8 weeks of remedy, echocardiography, hemodynamic parameters, the volumetric fraction of collagenous fibre （CVF） and oxidative stress including total antioxidation capacity（T-AOC） and malondialdehyde （MDA） were studied. Results： Compared with adriamycin group, carvedilol group can significantly improve left ventricular ejection fraction（ P 〈 0.01 ） and depress CVF obviously （ P 〈 0.01 ）. Compared with control group, adriamycin group can significantly decrease the activity of T-AOC（ P 〈 0.01 ） and improve the contents of MDA greatly（P 〈0.01 ）. The activity of T-AOC in the carvedilol group was enhanced significantly compared with that in the adriamycin group（P 〈0.01 ）. The contents of MDA in the carvedilol group were decreased compared with that in the adriamycin group（ P 〈0.05 ）. Conclusion： Carvedilol can relieve adriamycin-induced hemodynamic abnormality evidently, improve cardiac systolic and diastolic function greatly and reverse ventricular remodeling. This mechanism may be concerned with its improvement to oxygen stress.