四逆汤抗阿霉素性心力衰竭的超氧化物歧化酶机制探讨

Protective effects of Sini decoction on Adriamycin-induced heart failure and its mechanism: role of superoxide dismutase

目的:探讨超氧化物歧化酶(SOD)在阿霉素(ADR)诱导的心力衰竭中的作用以及四逆汤的可能的保护机制。方法:SD大鼠随机分为对照组,心衰组和四逆汤组,心衰组和四逆汤组尾静脉注射ADR复制心衰模型,四逆汤组给予四逆汤煎剂灌胃(含生药3.75 g·kg-1·d-1),实验结束时测定各组大鼠心功能,留取心肌组织并提取心肌细胞线粒体,以TBA法测定丙二醛(MDA)含量,邻苯三酚法测定SOD活性,RT-PCR法检测铜-锌SOD和锰SOD mRNA表达情况。结果:与对照组相比,心衰组大鼠心脏左室内压及左室内压变化速率明显降低,左室舒张末期压力明显增高,心肌组织铜.锌SOD和锰SOD活性及其mRNA表达明显降低,心肌组织和心肌细胞线粒体MDA含量明显增多;而四逆汤组可以显著改善心衰大鼠心功能,并提高铜-锌SOD和锰SOD的活性,增加其mRNA表达,并明显减少心肌组织和心肌细胞线粒体MDA的含量。结论:阿霉素性心力衰竭中心肌细胞线粒体存在明显的氧化应激反应,四逆汤可以改善心功能,减轻此氧化应激反应,其机制可能与提高SOD活性密切相关。

Objective: To investigate the role of superoxide dismutase (SOD) in Adriamycin (ADR)-induced heart failure and the protective effects of Sini decoction (SND). Method: SD rats were randomly divided into three groups, control group, heart failure group and SND group. ADR was injected in the rats of heart failure group and SND group by caudal vein. After injection, the rats in SND group were given SND (3.75 g·kg-1d-1, p.o.). Three weeks later, cardiac function, content of malondialdehyde (MDA) of both myocardium and mitochondria and activity of Cu-Zn SOD and Mn SOD were measured. The mRNA expression of Cu-Zn SOD and Mn SOD were also detected by RT-PCR. Result: Compared with control group, LVSP and ± dp/dt max were obviously decreased, while LVEDP was markedly increased in the heart failure group. The mRNA expression and the activity of Cu-Zn SOD and Mn SOD in heart failure group were obviously lower than that in the controls'. In addition, the MDA content of both myocardium and mitochondria were clearly increased in heart failure rats. In SND-treated rats, the cardiac function, the activity and the mRNA expression of Cu-Zn SOD and Mn SOD were significantly elevated and the content of MDA was reduced, which had no statistic difference with the rats in control group. Conclusion: The data suggest that oxidative stress is present in the mitochondria of myocardium in ADR-induced heart failure rats and it can be eased by SND. The mechanism may be closely related to SOD.