参附益心颗粒对心力衰竭大鼠心肌ATP含量及解偶联蛋白-2的影响

Effects of Shenfu Yixin Granules on the content of ATP and expression of uncoupling protein-2 in rats with heart failure

目的:观察参附益心颗粒对心力衰竭大鼠心肌组织三磷酸腺苷(ATP)含量及解偶联蛋白-2(UCP-2)表达的影响。方法:采用结扎大鼠左冠状动脉前降支的方法复制心肌梗死后心力衰竭大鼠模型。实验共设5组:假手术组,模型组,参附益心颗粒常用剂量组、高剂量组和氯沙坦组。其中假手术和模型组给予相同体积的蒸馏水灌胃,药物干预组将相应药物溶于蒸馏水后经口灌胃给药,4周后利用超声评价左室舒张末内径(LVEDD)、左室收缩末内径(LVESD)、左室射血分数(LVEF)和左室短轴缩短率(LVFS);采用生物发光法检测左心室缺血危险区组织的ATP含量;同时以JC-1为荧光分子探针检测大鼠心肌线粒体膜电位的变化;Western Blot确定心肌UCP-2的蛋白表达量。结果:与模型组比较,参附益心颗粒干预组心肌ATP含量及线粒体膜电位均显著升高(P<0.01,P<0.05),伴随心功能的改善,同时抑制UCP-2的蛋白表达(P<0.01,P<0.05)。结论:参附益心颗粒能够提高心衰大鼠心肌ATP含量、改善心脏功能,该作用可能与其抑制UCP-2的过表达和线粒体膜电位的降低有关。

Objective: To observe the effect of Shenfu Yixin Granules(SFYX) on the content of ATP and expression of uncoupling protein-2(UCP-2) in myocardial tissue of rats with heart failure(HF) induced by myocardial infarction(MI). Methods: HF was induced by the ligation of left anterior descending coronary artery in adult male Sprague-Dawley rats. Four weeks after MI, all rats were randomly divided into 5 groups: Sham-operated group, HF+vehicle groups, two groups of SFYX(low dose, high dose) and losartan group. All the medicines were given for 4 weeks by oral gavage once a day for 4 weeks after MI, and the rats in model group and sham-operated group were administered with the same volume of distilled water. The left ventricular end-diastolic dimension(LVEDD), left ventricular end-systolic dimension(LVESD), left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS) were measured by echocardiography at week 8 after MI. The content of ATP in the myocardial tissue and the mitochondrial membrane potential were determined by the bioluminescence method and JC-1 fluorescence probe method respectively. The expression of UCP-2 was determined by using Western Blot. Results: Compared to HF+vehicle group, SFYX enhanced systolic cardiac function. In addition, two SFYX groups significantly increased the content of ATP in the myocardial tissue and the mitochondrial membrane potential(P<0.01, P<0.05), and the expression of UCP-2 was decreased(P<0.01, P<0.05). Conclusion: SFYX can enhance the content of ATP and improve cardiac function in rats with HF, which may be associated with the its inhibition of over expression of UCP-2 and decrease of mitochondrial membrane.