褪黑素对心力衰竭大鼠心肌细胞凋亡及氧化应激的影响

The influence of melatonin on the cardiomyocyte apoptosis and oxidative stress in rat with chronic heart failure

目的:观察褪黑素(melatonin,MT)对心力衰竭大鼠的心肌细胞凋亡及氧化应激的影响,并初步探讨其影响机制。方法:将52只雄性SD大鼠随机分为3组。MT组及异丙肾上腺素组(ISO组)各20只,对照组12只。MT组及ISO组给予ISO皮下多点注射ISO建立心衰模型,造模成功后MT组给予MT治疗,ISO组不给予MT治疗;对照组不给予任何处置。8周后,随机从各组选取存活大鼠各10只,进行心脏超声检查,并测定心肌组织SOD、GSH-PX活性及MDA的含量;原位末端标记法(TUNEL)检测心肌细胞凋亡指数。结果:与对照组大鼠比较,ISO组及MT组大鼠LVEDD、LVESD明显扩大(P<0.05或P<0.01),LVEF、FS明显降低(P<0.01),心肌细胞凋亡指数升高(P<0.01),心肌组织MDA含量升高(P<0.01),SOD、GSH-Px活性均有显著性下降(P<0.05或0.01);与ISO组大鼠比较,MT组大鼠LVEDD、LVESD明显减小(P<0.05),LVEF、FS明显增加(P<0.05),心肌细胞凋亡指数减低(P<0.01),心肌组织MDA含量下降(P<0.05),SOD、GSH-Px活性亦有明显升高(P<0.05)。结论:MT能够改善心力衰竭大鼠心肌组织的氧化应激反应及心肌细胞凋亡,并具有改善心脏功能的作用。

Objective： To investigate the influence of melatonin on the cardiomyocyte apoptosis and oxidative stress in rat with chronic heart failure, and to discover its related mechanism. Methods： Fifty and two male SD rats were randomly divided into three groups： MT group （n=20）, ISO group （n=20） and control group （n=12）. Rats in MT group and ISO group were injected subeutaneously with isoproterenol （ISO）. The rats in control group were not administrated. Rat models of CHF in MT group treated with melatonin per day. 8 weeks later, echocardiogram, contents of myocardial malondildehyde （MDA）, activities of myocardial superoxide dismutase （SOD） and ghutathione peroxidase （GSH-Px）, index of cardiomyocyte apoptosis were carried out. Results： Compared with the control group, the LVEDD, LVESD enlarged （P〈0.05 or 0.01）, the LVEF, FS decreased （P〈0.01）, the index of cardiomyocyte apoptosis and contents of myocardial MDA increased distinctly （P〈0.01）, the activities of myocardial SOD and GSH-Px significantly decreased （P〈0.05） in ISO group and MT group. Compared with the ISO group, the LVEDD, LVESD decreased （P〈0.05）, the LVEF, FS enlarged （P〈0.05）, the index of cardiomyocyte apoptosis and contents of myocardial MDA decreased （P〈0.05 or 0.01）, the activities of myocardial SOD and GSH-Px signif- icantly increased （P〈0.05） in MT group. Conclusion： MT could exert a protective effect on ISO-induced chronic heart failure rats through decreasing oxidative stress of myocardial tissue and cardiomyocyte apoptosis.