硫辛酸对多柔比星致大鼠心肌细胞损伤凋亡的保护作用研究  

Protective Effects of Lipoic Acid on Myocardial Cell Apoptosis Induced by Doxorubicin in Rats

作　　者：张志刚[1] 陈建忠[1] 欧扬[2] 刘平[1] 

机构地区：[1]聊城市人民医院药学部,山东聊城252000 [2]山东大学齐鲁医院药学部,济南250000

出　　处：《中国药房》2013年第13期1180-1182,共3页China Pharmacy

摘　　要：目的:研究硫辛酸对多柔比星致大鼠心肌细胞损伤凋亡的保护作用。方法:将大鼠随机分为正常对照组、模型组和低、中、高剂量[10、20、40mg(/kg·d)]硫辛酸组,每组10只,后4组腹腔注射多柔比星3mg/kg,隔日1次,连用6次建模。硫辛酸组于注射多柔比星第2天起腹腔注射相应浓度的硫辛酸,每日1次,连用10d。多柔比星末次给药24h后处死大鼠,观察各组大鼠心肌结构变化,检测心肌细胞凋亡情况和心肌细胞中抑制细胞凋亡因子Bcl-2、凋亡基因Bax蛋白表达情况。结果:与正常对照组比较,模型组大鼠肌丝排列疏松、紊乱,大部分线粒体形成空泡,其心肌细胞凋亡指数和Bax蛋白表达均明显增强,Bcl-2蛋白表达明显降低(P<0.01);与模型组比较,低、中、高剂量硫辛酸组心肌细胞病理形态学变化均改善,且凋亡指数和Bax蛋白表达均明显降低,Bcl-2蛋白表达明显增强(P<0.01)并呈剂量依赖性。结论:硫辛酸可拮抗多柔比星所致大鼠心肌细胞损伤,其作用机制可能与抑制Bax蛋白表达、增强Bcl-2蛋白表达有关。OBJECTIVE：To study the protective effect of lipoic acid（LA）on doxorubicin-induced myocardial cell apoptosis in rats.METHODS：Rats were randomized into normal control group,model group and LA low-dose,medium-dose and high-dose groups [10,20,40 mg（/kg · d）] with 10 rats in each group.Latter 4 groups were given doxorubicin 3 mg/kg by intraperitoneal injection once a day for 6 times to establish model.LA groups were given corresponding concentrations of LA intraperitoneally after 2 days once a day for consecutive 10 days.Those rats were sacrificed 24 h after last administration.The changes of myocardial structure were observed,and myocardial cell apoptosis,the protein expressions of Bax and Bcl-2 were detected.RESULTS：Compared with normal control group,loose and disordered myofilament arrangement were found in model group,most of mitochondria vacuoles formed,apoptosis index and the protein expressions of Bax increased significantly,but the protein expressions of Bcl-2 decreased（P0.01）;compared with model group,pathomorphology change of cardiac cell in LA groups improved and apoptosis index and the protein expressions of Bax decreased significantly while the protein expressions of Bcl-2 increased in dose-dependant manner（P0.01）.CONCLUSIONS：LA could suppress the myocardial cell apoptosis induced by doxorubicin,which may be related to the expression down-regulation of Bax and expression up-regulation of Bcl-2.

关 键 词：硫辛酸 多柔比星 大鼠 心肌细胞 凋亡 Bcl-2 BAX 表达 

分 类 号：R965[医药卫生—药理学]