黄芪甲苷衍生物ASId治疗慢性心力衰竭的机制研究

目的探讨黄芪甲苷衍生物ASId治疗慢性心力衰竭的作用机制。方法大鼠、犬提取心肌细胞膜检测酶活性;大鼠结扎冠脉引起心肌梗死后取左心室,利用免疫组织化学检测心肌肥厚信号转导通路的钙调神经磷酸酶（calcineurin,CaN）表达情况。结果 ASId对大鼠和犬心肌细胞膜Na＋/K＋-ATPase均有抑制作用,其IC50分别为（1.58±0.27）×106和（1.41±0.16）×107mol/L,在受试剂量下（108～105mol/L）对Ca2＋/Mg2＋-ATPase活性无明显抑制作用;免疫组化研究表明,ASId0.5、1.0mg/kg可显著降低CaN表达,与模型对照组比较,其表达分别下降73.1%（P〈0.01）、78.0%（P〈0.001）,提示ASId抗心肌肥厚机制与抑制心肌肥厚信号转导通路的重要关键因子CaN有关。结论 ASId治疗心衰机制与Na＋/K＋-ATPase抑制产生的即刻心肌收缩效应,以及抗心肌肥厚的远期效应有关。

Mechanisms of astragaloside IV derivative on chronic heart failure

Objective To study the mechanisms of astragaloside IV derivative （ASId） used in the treatment of the chronic heart failure. Methods The myocardial cell membrane was extracted from rats and dogs and the enzyme activity was detected. The calcineurin phosphatase （calcineurin, CaN） expression of signal transduction pathways of myocardial hypertrophy in left ventricle from myocardial infarction rats was also detected by immunohistochemistry. Results The Na＋/K＋-ATPase activity from both rats and dogs were inhibited except for Ca2＋/Mg2＋-ATPase activity at the dose of 10 8-10 5 mol/L. The IC50 values were （1.58 ± 0.27） × 10 6 and （1.41 ± 0.16） × 10 7 mol/L, respectively. ASId （0.5 and 1.0 mg/kg） could significantly decrease CaN expression by 73.1% （P 0.01） and 78.0% （P 0.001） compared with the control group, which could indicate that the role of ASId on myocardial hypertrophy may be related with CaN, and the key factor of signal transduction pathways of myocardial hypertrophy. Conclusion The mechanism of ASId on heart failure is concerned with the immediate myocardial contraction by inhibiting Na＋/K＋-ATPase, as well as the long-term effects by relieving myocardial hypertrophy.