基于ACE2-Ang(1-7)-Mas受体轴探讨益气强心汤对心衰大鼠的作用机制研究

Study on the Mechanism of Yiqi Qiangxin Decoction on Heart Failure Rats Based on ACE 2-Ang(1-7)-Mas Receptor Axis

目的:以益气强心汤为研究对象,从对RAS系统影响角度,探讨该方对压力负荷心衰大鼠心肌重塑的影响及其可能机制。方法:以SPF级雄性Wistar大鼠为研究对象,微创主动脉缩窄法制备压力负荷心力衰竭动物模型,设立假手术组、动物模型组、西药治疗组、中药治疗组,在治疗前后检测血清Ang(1-7)、AngⅡ;术后8周检测各组心肌组织ACE2、Mas的蛋白表达水平;行左室组织切片,经染色处理,观察各组心肌重塑程度。结果:(1)模型组心肌纤维化明显加重,而经西药或益气强心汤治疗后大鼠心肌纤维化程度明显减轻。中药组较西药组疗效更加明显。(2)术后模型组、西药组、中药组AngⅡ水平均较假手术组明显升高,具有统计学意义(P<0.01),药物干预后4周,模型组AngⅡ水平较术后无明显改变(P>0.05),西药组及中药组AngⅡ水平较术后有下降,差异具有统计学意义(P<0.01);药物干预后8周,西药组、中药组AngⅡ水平较模型组明显下降,具有统计学意义(P<0.01)。(3)术后其余各组Ang(1-7)水平均较假手术组下降,具有统计学意义(P<0.05),药物干预后4周,模型组Ang(1-7)水平较术后有所下降,具有统计学意义(P<0.05),西药组及中药组Ang(1-7)水平较术后明显升高,差异具有统计学意义(P<0.01),中药组及西药组间Ang(1-7)水平差异具有统计学意义(P<0.01)。药物干预后8周,西药组、中药组Ang(1-7)水平较模型组明显升高,具有统计学意义(P<0.01)。(4)模型组ACE2的表达量较假手术组明显下降,差异具有统计学意义(P<0.05);西药组及中药组ACE2的表达量均较模型组明显升高,差异具有统计学意义(P<0.01);西药组及中药组间差异无统计学意义(P>0.05)。(5)模型组Mas的表达量较假手术组有所升高,差异无统计学意义(P>0.05);西药组及中药组Mas的表达量均较模型组明显升高,差异具有统计学意义(P<0.01);西药组及中药组间差异无统计学意义(P>0.05)。结论:益气强心汤对压力负荷心衰大鼠的心肌重塑有干预作用,益气强心汤对压力负荷心衰大鼠Ang(1-7)、AngⅡ、ACE2及Mas具有调节作用。

Objective:To explore the possible mechanism of Yiqi Qiangxin Decoction(YQQXD)on myocardial remodeling in rats with pressure overload heart failure from the perspective of its effect on RAS system.Methods:SPF male Wistar rats were selected as the research object.The pressure overload heart failure animal model was prepared by minimally invasive aortic coarctation.Sham operation group,animal model group,western medicine treatment group and traditional Chinese medicine treatment group were established.Serum Ang(1-7)and AngⅡwere detected before and after treatment,and the expression of ACE2 and Mas protein in myocardial tissue was detected 8 weeks after operation.Left ventricular tissue sections were made and stained to observe the degree of myocardial remodeling in each group.Result:(1)Myocardial fibrosis in model group was aggravated significantly,while the degree of myocardial fibrosis in rats was significantly reduced after treatment with western medicine or,Yiqi Qiangxin Decoction.The curative effect of traditional Chinese medicine group is more obvious than that of Western medicine group.(2)AngⅡlevels in model group,western medicine group and traditional Chinese medicine group were significantly higher than those in sham operation group(P<0.01).Four weeks after drug intervention,AngⅡlevels in model group did not change significantly compared with those after operation(P>0.05).AngⅡlevels in western medicine group and traditional Chinese medicine group were significantly lower than those after operation(P<0.01).Eight weeks after drug intervention,AngⅡlevel in western medicine group and traditional Chinese medicine group was significantly lower than that in model group(P<0.01).(3)Ang(1-7)levels in the other groups were lower than those in the sham-operated group(P<0.05).Ang(1-7)levels in the model group were lower than those in the sham-operated group 4 weeks after drug intervention(P<0.05).Ang(1-7)levels in the western medicine group and the traditional Chinese medicine group were significantly higher than those in the sham-operated group(P<0.05).The difference was statistically significant.Significance(P<0.01),Ang(1-7)level between Chinese medicine group and Western medicine group had statistical significance(P<0.01).Eight weeks after drug intervention,Ang(1-7)level in western medicine group and traditional Chinese medicine group was significantly higher than that in model group(P<0.01).(4)The expression of ACE2 in the model group was significantly lower than that in the sham-operated group(P<0.05);the expression of ACE2 in the western medicine group and the traditional Chinese medicine group was significantly higher than that in the model group(P<0.01);there was no significant difference between the western medicine group and the traditional Chinese medicine group(P>0.05).(5)The expression of Mas in the model group was higher than that in the sham-operated group,with no significant difference(P>0.05);the expression of Mas in the western medicine group and the traditional Chinese medicine group was significantly higher than that in the model group(P<0.01);there was no significant difference between the western medicine group and the traditional Chinese medicine group(P>0.05).Conclusion:Yiqi Qiangxin Decoction has intervention effect on myocardial remodeling in rats with pressure overload heart failure.Yiqi Qiangxin Decoction can regulate Ang(1-7),AngⅡ,ACE2 and Mas in rats with pressure overload heart failure.