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目的探讨探讨芪苈强心胶囊是否通过抑制血管紧张素Ⅱ(AngⅡ)表达改善压力超负荷下小鼠心肌肥厚。方法小鼠行升主动脉缩窄手术(TAC)建立心肌肥厚模型,8-10周龄野生型雄性小鼠(WT)和雄性血管紧张素原基因敲除小鼠(ATG-/-)随机分为假手术组、生理盐水组、芪苈强心胶囊三组,TAC组小鼠给予生理盐水或1.0mg/(kg.d)药物灌胃处理。术后2周行心超及血流动力学检查,同时分析心肌组织学指标以及肥厚相关基因表达,酶联免疫吸附法(ELISA)检测血浆和心肌组织AngⅡ浓度,,蛋白印迹法检测磷酸化细胞外信号调节激酶(p-ERK)及血管紧张素Ⅱ-1型(AT1)受体表达。结果 WT和ATG-/-小鼠TAC后2周,主动脉血压及左室收缩末期压显著升高,芪苈强心胶囊对其均无影响。WT小鼠中,此药显著抑制TAC介导AngⅡ的升高(P<0.05),抑制TAC介导的左室前壁,左室后壁增厚以及心肌细胞横截面积(CSA)和纤维化面积增大,同时抑制肥厚相关基因、AT1受体和p-ERK表达上调(P<0.05),;ATG-/-小鼠中,在AngⅡ缺失的情况下,TAC两组间左室前后壁、CSA、纤维化面积以及肥厚相关基因、AT1受体和p-ERK表达无明显差异(P>0.05)。结论芪苈强心胶囊改善压力超负荷致小鼠心肌肥厚是通过抑制AngⅡ表达来减弱AT1受体激活,非直接抑制压力超负荷机械刺激引起AT1受体的激活。
Objective To investigate whether Qili Qiangxin capsule can improve cardiac hypertrophy in mice under pressure overload by inhibiting the expression of angiotensin Ⅱ (Ang Ⅱ). Methods The model of cardiac hypertrophy was established by ascending aorta stenosis (TAC). Eight to ten weeks old wild-type male mice (WT) and male angiotensinogen knockout mice (ATG - / -) were randomized The sham operation group, saline group and Qiqiangqiangxin capsule were given three groups. The mice in TAC group were treated with saline or 1.0mg / (kg · d) of drug. Hyperalgesia and hemodynamics were performed 2 weeks after operation. The myocardial histological parameters and the expression of hypertrophy related genes were also analyzed. The concentrations of Ang Ⅱ in plasma and myocardium were detected by enzyme-linked immunosorbent assay (ELISA), and the phosphorylated extracellular signal Regulated kinase (p-ERK) and angiotensin II-1 (AT1) receptor expression. Results The aortic pressure and left ventricular end-systolic pressure were significantly increased in WT and ATG - / - mice two weeks after TAC, and Qiliqiangxin capsule had no effect on it. WT mice, the drug significantly inhibited TAC-mediated elevation of Ang II (P <0.05), inhibited TAC-mediated left ventricular anterior wall, left ventricular posterior wall thickening and myocardial cell cross-sectional area (CSA) and fibrosis (P <0.05); ATG - / - mice, in the absence of AngⅡ, TAC between the two groups before and after the left and right walls, CSA, fibrosis area, hypertrophy related gene, AT1 receptor and p-ERK expression had no significant difference (P> 0.05). Conclusion Qili Qiangxin Capsule can reduce the activation of AT1 receptor by inhibiting the expression of Ang Ⅱ, and not directly inhibit the activation of AT1 receptor induced by pressure overload mechanical stimulation.