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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-induced heart failure and the possible protective mechanism of SND. METHODS: Sprague-Dawley rats were randomly divided into control group, heart failure group and Sini decoction group, heart failure group and Sini Tang group. ADR was used to induce heart failure model. Sini Decoction group was given SND decoction by gavage ( Containing crude drug 3.75 g·kg-1·d-1), at the end of the experiment, the heart function was measured in each group. Myocardial tissue was extracted and myocardial cell mitochondria were extracted. Malondialdehyde (MDA) content was measured by TBA method. SOD activity was determined by phenol method, and the expression of copper-zinc SOD and manganese SOD mRNA was detected by RT-PCR. RESULTS: Compared with the control group, the changes of left ventricular pressure and left ventricular pressure in heart failure rats were significantly lower, the left ventricular end-diastolic pressure was significantly increased, and the activities of copper, zinc superoxide dismutase and manganese superoxide dismutase in myocardial tissue were significantly decreased. The mitochondrial MDA content in myocardium and myocardial cells increased significantly; while Sini Decoction significantly improved heart function in rats with heart failure, increased activity of copper-zinc SOD and manganese SOD, increased its mRNA expression, and significantly reduced myocardial tissue and Mitochondrial MDA content in myocardial cells. Conclusion: There is a significant oxidative stress reaction in mitochondria of cardiomyocytes in adriamycin-induced heart failure. Sini Decoction can improve cardiac function and alleviate this oxidative stress reaction. Its mechanism may be closely related to the increase of SOD activity.