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目的:研究卡维地洛对阿霉素心肌病兔氧化应激的影响,并探讨氧化应激与慢性心肌毒性之间的关系。方法:将40只日本长耳白兔随机分为对照组、阿霉素组、美托洛尔组和卡维地洛组,每组各10只。耳缘静脉注射阿霉素(每次1ml.kg-1,每周2次,共8周)建立阿霉素心肌病模型,对照组采用耳缘静脉注射0.9%氯化钠(每次1ml.kg-1,每周2次,共8周)。3周后,对照组和阿霉素组以0.9%氯化钠(5ml.kg-1.d-1)灌胃,美托洛尔组和卡维地洛组分别给予美托洛尔(5mg.kg-1.d-1)和卡维地洛(5mg.kg-1.d-1)灌胃。2个月后,超声心动图观察各组心脏结构变化,检测兔血清中丙二醛(MDA)、超氧化物岐化酶(SOD)和N末端前体脑钠肽(NT-proBNP)水平,并制备兔左室楔形心肌块的灌注模型,记录快频率程序刺激条件下室性心律失常的发生率。结果:与对照组比较,阿霉素组左室舒张末径(LVEDd)增大、左室射血分数(LVEF)降低(均P<0.05),血清SOD活性降低、NT-proBNP和MDA浓度升高,室性心律失常发生率增加(均P<0.05)。与阿霉素组比较,美托洛尔组无显著性变化,卡维地洛组LVEDd缩小、LVEF升高(均P<0.05),血清SOD活性增加、NT-proBNP和MDA浓度降低,室性心律失常发生率明显降低(均P<0.05)。结论:与美托洛尔比较,卡维地洛对阿霉素心肌病有保护作用,并能降低室性心律失常的发生,其机制与氧化自由基降低密切相关。
Objective: To study the effects of carvedilol on oxidative stress in adriamycin-induced cardiomyopathy rabbits and to explore the relationship between oxidative stress and chronic cardiotoxicity. Methods: Forty Japanese white rabbits were randomly divided into control group, doxorubicin group, metoprolol group and carvedilol group, with 10 rats in each group. A doxorubicin cardiomyopathy model was established by intravenous injection of doxorubicin (1ml.kg-1, twice a week for 8 weeks). The control group received 0.9% sodium chloride (1ml each time). kg-1 twice a week for a total of 8 weeks). Three weeks later, the control group and the doxorubicin group were orally administered with 0.9% sodium chloride (5ml.kg-1.d-1), the metoprolol group and the carvedilol group were given metoprolol kg-1.d-1) and carvedilol (5 mg.kg-1.d-1). After 2 months, the changes of cardiac structure in each group were observed by echocardiography. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and N-terminal pro-brain natriuretic peptide (NT-proBNP) The perfusion model of left ventricular wedge-shaped myocardial block was prepared and the incidence of ventricular arrhythmia was recorded under fast-frequency stimulation. Results Compared with the control group, left ventricular diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) in adriamycin group decreased (all P <0.05), serum SOD activity decreased, NT-proBNP and MDA levels increased The incidence of high and ventricular arrhythmias increased (all P <0.05). Compared with doxorubicin group, there was no significant change in metoprolol group, LVEDd reduced and LVEF increased in carvedilol group (all P <0.05), serum SOD activity increased, NT-proBNP and MDA concentrations decreased, ventricular Arrhythmia incidence was significantly lower (all P <0.05). CONCLUSION: Compared with metoprolol, carvedilol has a protective effect on doxorubicin cardiomyopathy and can reduce the occurrence of ventricular arrhythmia, and its mechanism is closely related to the reduction of oxidative free radicals.