黄芪多糖抑制血管紧张素Ⅱ诱导心肌肥大的作用途径

Pathways of astragalus polysaccharide inhibiting angiotensin Ⅱ-induced cardiac hypertrophy

背景:黄芪多糖是中药材黄芪中重要的天然有效成分,具有抗应激、抗氧化、抗自由基和降血糖等药理作用。目的:分析黄芪多糖对血管紧张素Ⅱ诱导心肌肥大的作用及可能的机制。方法:大鼠心肌细胞株H9c2:中山大学实验中心馈赠。将培养的H9c2心肌细胞随机分为空白对照组,血管紧张素(10^(-6) mol/L)组;血管紧张素(10^(-6) mol/L)+黄芪多糖(10^(-6) mol/L)高浓度组;血管紧张素(10^(-6) mol/L)+黄芪多糖(10^(-7) mol/L)中浓度组;血管紧张素(10^(-6) mol/L)+黄芪多糖(10-8 mol/L)低浓度组。在体积分数10%FBS的DMEM培养液中培养48 h,检测H9c2心肌细胞表面积、蛋白浓度、细胞存活率及肥大相关基因心房利钠肽、脑利钠肽的mRNA表达,观察黄芪多糖对血管紧张素Ⅱ诱导的心肌肥大的作用。结果与结论:①与空白对照组相比,血管紧张素Ⅱ组H9c2心肌细胞表面积显著增加(P <0.05),加入黄芪多糖后,H9c2心肌细胞表面积减小,尤其黄芪多糖高浓度组心肌细胞表面积较空白对照组明显减小(P<0.05);②血管紧张素Ⅱ组细胞总蛋白含量及心肌细胞肥大相关基因的mRNA表达较空白对照组增加(P<0.05),黄芪多糖高浓度组H9c2心肌细胞总蛋白含量及黄芪多糖高、中浓度组心肌细胞肥大相关基因的mRNA的表达显著下调(P <0.05);③与血管紧张素组相比,黄芪多糖高、中浓度组能明显提升心肌细胞存活率(P <0.05);④结果说明,黄芪多糖可有效抑制血管紧张素Ⅱ诱导的心肌细胞肥大。

BACKGROUND: Astragalus polysaccharide, an important ingredient of astragalus, exerts pharmacological effects of anti-stress, anti-oxidation, anti-free radical and can reduce blood glucose. OBJECTIVE: To explore the effect of astragalus polysaccharide on angiotensin Ⅱ-induced cardiac hypertrophy and the underlying mechanism. METHODS: H9c2 cardiomyocytes were provided by Experimental Center of Sun Yat-sen University, and then randomly divided into control group, angiotensin Ⅱ(10-6 mol/L) group, angiotensin Ⅱ(10-6 mol/L)+astragalus polysaccharide(10-6 mol/L) group, angiotensin Ⅱ(10-6 mol/L) +astragalus polysaccharide(10-7 mol/L) group, and angiotensin Ⅱ(10-6 mol/L)+astragalus polysaccharide(10-8 mol/L) group. The cells were cultured in the DMEM containing 10% fetal bovine serum for 48 hours. The surface area of cardiomyocytes, protein concentration, cell viability, and the mRNA expression of hypertrophy-related genes atrial natriuretic peptide and brain natriuretic peptide were detected to investigate the effect of astragalus polysaccharide on angiotensin Ⅱ-induced cardiac hypertrophy. RESULTS AND CONCLUSION:(1) Compared with the control group, angiotensin Ⅱ significantly increased the surface area of H9c2 cardiomyocytes(P < 0.05). The cell area was significantly decreased after addition of astragalus polysaccharide compared with the control group, especially 10-6 mol/L astragalus polysaccharide(P < 0.05).(2) The total protein content and expression level of hypertrophy-related genes in the angiotensin Ⅱ group were significantly higher than those in the control group. The total protein content and expression level of hypertrophy-related genes in the angiotensin Ⅱ(10-6 mol/L)+astragalus polysaccharide(10-6 mol/L) and angiotensin Ⅱ(10-6 mol/L)+astragalus polysaccharide(10-7 mol/L) groups were significantly down-regulated(P < 0.05).(3) Compared with the angiotensin Ⅱ group, the survival rate of cardiomyocytes was increased significantly in the angiotensin Ⅱ(10-6 mol/L)+astragalus polysaccharide(10-6 mol/L) and angiotensin Ⅱ(10-6 mol/L)+astragalus polysaccharide(10-7 mol/L) groups(P < 0.05).(4) These results indicate that astragalus polysaccharide can effectively improve cardiac hypertrophy induced by angiotensin Ⅱ.