α-硫辛酸抗心肌肥厚作用

Protective Effects of Alpha-Lipoic Acid on Isoproterenol-induced Myocardial Hypertrophy in Rats

目的研究α-硫辛酸(α-LA)抗异丙肾上腺素致大鼠心肌肥厚的作用。方法 24只大鼠随机分为模型组、对照组、硫辛酸组,每组8只。模型组和硫辛酸组建立心肌肥厚模型,硫辛酸组同时给予α-硫辛酸盐液腹腔注射,100 mg·kg-1·d-1,qd。测定大鼠全心质量指数(HW/BW)、左心室质量指数(LVW/BW,即LVI),放射免疫分析法和逆转录聚合酶链反应(RT-PCR)检测大鼠心肌组织血管紧张肽Ⅱ(AngⅡ)、AT1R含量及AT1mRNA表达水平,硫代巴比妥酸法测定丙二醛(MDA)含量,黄嘌呤氧化酶法测定超氧化物歧化酶(SOD)活性。结果与对照组比较,模型组大鼠HW/BW、LVI明显升高,心肌AngⅡ、AT1R含量及AT1mRNA表达水平增高,心肌和血清MDA含量增高,SOD含量降低(P<0.01);与模型组比较,硫辛酸组各心脏指标均明显减低,心肌组织MDA、AngⅡ、AT1R含量及AT1mRNA表达水平降低,SOD含量增高(P<0.01)。结论氧化应激参与心肌肥厚的发生发展,α-LA通过抗氧化作用抑制心肌肥厚的发生发展。

Objective To investigate the protective effects of alpha-lipoic acid on isoproterenol（Iso）-induced myocardial hypertrophy in rats.Methods Twenty-four rats were randomly and evenly divided into 3 groups： control group,model group and alpha-lipoic acid（LA） group.Myocardial hypertrophy model of rats were induced by injection of Iso（1 mg·kg^-1,ip） once daily for 15 days.The control group was treated with the same volume of normal saline injection.The LA group according to the above method was injected with the alpha lipoic acid in the abdominal cavity at 100 mg·kg^-1·d^-1 once daily for 15 days.The heart-weight（HW）,left ventricular weight（LVW）,the ratios of HW/BW and LVW/BW（LVI） were measured.The content of angiotensin（AngII） and the expression of angiotensin type one receptor（AT1R） in the left ventricle were determined by radioimmunoassay and immunochemistry,respectively.Reverse transcription-polymerase chain raction（RT-PCR） was used to detect the expression of AT1 receptor mRNA of the left ventricular myocardial tissue.Thiobarbituric acid method and xanthineoxidase method were used to determine the contents and activities of malondialdehyde（MDA） and superoxide dismutase（SOD） in the myocardial tissue,respectively.Results The HW/BW,LVI and the content of AngII and the expression of AT1R mRNA in the left ventricle significantly increased in the model group as compared with the control group.The content of MDA in the left ventricle and blood was increased but SOD decreased（P〈0.01）.The cardiac indices were decreased significantly,the content of MDA and Ang II,the expression of AT1R and AT1 mRNA decreased in the LA group as compared with the model group,but the content of SOD was increased（P〈0.01）.Conclusion Oxidative stress is involved in the development of myocardial hypertrophy.α-LA is shown to prevent remodeling of Iso-induced myocardial hypertrophy in rats through antioxidation.