参麦注射液对大鼠心肌肥大模型血管紧张素Ⅱ介导的钙调神经磷酸酶通路的干预效应

Effects of Shenmai Injection on Calcineurin Signal Pathway Mediated by Angiotensin Ⅱ in Cardiac Hypertrophy of Rats

目的探讨血管紧张素Ⅱ(AngⅡ)介导的钙调神经磷酸酶(CaN)信号通路在大鼠心肌肥大中的作用,及参麦注射液逆转心肌肥厚可能的分子机制。方法腹主动脉缩窄法建立压力超负荷大鼠心肌肥大模型。实验动物按随机原则分为模型组、假手术组、参麦注射液治疗组、缬沙坦治疗组。放免法测定血清和心肌组织中的AngⅡ的含量,测定左室质量指数、心系数,应用免疫印迹(Western blot)法检测CaN蛋白表达。结果与假手术组比较,其它各组左室质量指数和心系数明显升高;缬沙坦组、参麦注射液组左室质量指数和心系数明显低于模型组。模型组、缬沙坦组、参麦注射液组血浆AngⅡ含量均高于假手术组;模型组、参麦注射液组心肌AngⅡ含量均高于假手术组;与模型组比较,缬沙坦组血浆AngⅡ含量显著升高,心肌AngⅡ含量降低。模型组CaN蛋白表达量显著高于假手术组,参麦注射液组、缬沙坦组CaN蛋白表达量低于模型组。结论证实过度激活的肾素血管紧张素(RAS)系统是心肌肥大发生发展的重要机制之一,AngⅡ介导的CaN信号通路在压力超负荷大鼠心肌肥大中起重要作用;参麦注射液对CaN信号通路致心肌肥大有抑制作用。

Objective： To investigate the effect of the calcineurin signal pathway mediated by Angiotensin Ⅱ （Aug Ⅱ） in cardiac hypertrophy of rats and the molecular mechanism of Shenmai Injection on reversal cardiac hypertrophy. Methods： The models of cardiac hypertrophy induced by pressure overload established by transverse aortic eoarctation were divided randomly into five groups： model group, sham operated group, Shenmai Injection group, valsartan group. Some indexes were detected including： the concentration of Ang Ⅱ in both serum and myocardium mea- sured by radioimmunoassay method, the left ventricular mass index, the cardiac coefficient and the expression of CaN protein by Western blot. Results： Compared with the sham operated group, the cardiac coefficient and left ventricular mass indexes of other groups ascended obviously. Those indexes of the valsartan group and the Shenmai Injection group were obviously less than that of model group. The concentrations of serum Ang Ⅱ in the model group, the valsartan group, the Shenmai Injection group were more than that of sham operated group. The concentrations of myocardium Ang Ⅱ in the model group and the Shenmai Injection group were more than that of sham operated group, Meanwhile, compared with the model group, the concentration of serum Ang Ⅱ raised significantly, but the myocardium Ang Ⅱ fell obviously. The expression of CaN in the model group was higher than that of in the sham operated group significant- ly. The expressions of CaN in the valsartan group and the Shenmai Injection group were lower than that of CaN in the model group. Conclusion：RAS system has an effect on hyptertrophied myocardium induced by pressure overloaded in rats. Calcineurin signal pathway mediated by Ang Ⅱ has the effect on hyptertrophied myocardium induced by pressure overloaded in rats. Shenmai Injection could inhibit the cardiac hypertrophy caused by the calcineurin signal pathway.