【摘要】 目的探讨卡维地洛对阿霉素心脏毒性的保护作用及可能的机制。方法将Wistar大鼠随机分为3组:阿霉素组、卡维地洛组和对照组,每组12只。(1)阿霉素组:腹腔注射阿霉素,每次2.5 mg/kg,4次/周,连续2周,累积剂量为20 mg/kg;用等量生理盐水灌胃8周。(2)卡维地洛组:腹腔注射阿霉素,剂量同阿霉素组;用卡维地洛每天30 mg/kg,分2次灌胃,共8周。(3)对照组:腹腔注射与阿霉素组等量的生理盐水,用等量生理盐水灌胃。第9周检测大鼠血流动力性和血清中超氧化物歧化酶(SOD)的活性和丙二醛(MDA)含量,检测心肌细胞凋亡情况。结果(1)血流动力学监测:卡维地洛组与阿霉素组相比,左心室压力上升和下降最大速率(±dp/dtmax)提高,左室舒张末压(LVEDP)的降低,差异均有统计学意义(均P<0.05),但左室收缩压(LVSP)、平均动脉压(MAP)差异无统计学意义(均P>0.05)。卡维地洛组与对照组相比,仅LVSP和MAP的差异有统计学意义(均P<0.05)。(2)血清中的SOD活性、MDA含量:卡维地洛组与阿霉素组相比,SOD活性增加,MDA含量降低,差异均有统计学意义(均P<0.05)。卡维地洛组与对照组相比,SOD和MDA含量的差异均无统计学意义(均P>0.05)。(3)心肌细胞凋亡情况:阿霉素组细胞凋亡较对照组增加,而卡维地洛组比阿霉素组减少,差异有统计学意义(均P<0.05)。结论卡维地洛能改善阿霉素引起的血流动力性异常,主要表现为改善心脏收缩与舒张功能;卡维地洛能抑制阿霉素引起的机体内过度的氧化应激;卡维地洛能减轻阿霉素引起的心肌细胞凋亡。更多还原

【Abstract】 Objective The study aims to explore the protective effects of carvedilol on the adriamycin-induced rat cardiotoxicity and to explore its possible mechanism.Methods Wistar rats weighing(270±10)g were randomly divided into three groups(n=12 in every group):adriamycin group,carvedilol group and control group.Adriamycin(2.5 mg/kg) was administered to rats in eight equal intraperitoneal injections over a period of 2 weeks(cumulative dose of 20 mg/kg)in adriamycin group and normal saline(30 mg/kg daily) was administered orally in twe equal doses every days over a 8-week period.Carvedilol(30 mg/kg daily) was administered orally in two equal doses every day over a 8-week period with adriamycin treatment in carvedilol group.The equivalent volume of normal saline was used in control group.In 9 week,the changes of rat cardiac function,the activity of superoxide dismutase and the contents of malondialdehyde in serum as well as myocardial cell apotosis were detected.Results(1) Hemodynamic effects:Compared with the control group,hemodynamic parameters in the adriamycin group were deteriorated(P<0.05).Compared with adriamycin group,±dp/dtmas were increased(P<0.05) and LVEDP was decreased(P<0.05) in the carvedilol group,but there was no significant difference in LVSP and MAP were not different from that in the adriamycin group(P>0.05).Defference in ±dp/dtmax and LVEDP in the carvedilol group and control group were not significant(P>0.05).(2)The activity of superoxide dismutase and the contents of malondialdehyde in serum.The activity of superoxide dismutase in the carvedilol group was enhanced significantly compared with that in the adriamycin group(P<0.05),the contents of malondialdehyde in the carvedilol group were decreased significantly compared with that in the adriamycin group(P<0.05).Diference in activity of superoxide dismutase and the contents of malondialdehyde between the carvedilol group and control group was not significant(P>0.05).(3) Cardiomyocyte apoptosis:Cardiomyocyte apoptosis in the adriamycin group were significantly increased compared with that in the control group (P<0.05),but cardiomyocyte apoptosis in the carvedilol group was lower than that in the adriamycin group(P<0.05).Conclusion(1)Carvedilol relieves adriamycin-induced hemodynamic abnormality mainly by improving cardiac systolic and diastolic function.(2)Carvedilol prevents adriamycin-induced excessive oxidative stress.(3)Carvedilol suppresses cardiomyocyte apoptosis is induced by adriamycin.更多还原