AAV9-Jumonji对慢性心力衰竭犬心脏肾素-血管紧张素-醛固酮系统活性的影响

Effect of AAV9-Jumonji on the activity of renin-angiotensin-aldosterone system in canine with chronic heart failure

目的:观察AAV9-Jumonji对慢性心力衰竭犬心脏,肾素-血管紧张素-醛固酮系统(RAAS)活性的影响,探讨其改善慢性心力衰竭的作用机制。方法:以杂种犬为研究对象,随机分为对照(control)组,心力衰竭(CHF)组,AAV9-Jumonji+心力衰竭(AAV9-Jumonji+CHF)组;超声心动图检查平均动脉压(mean artery pressure,MAP)和LVEF变化;酶联免疫法检测各组犬血清中ACE2、Ang II和collagen I的含量;q PCR和Western blot法检测各组犬心室肌组织中ACE2、Ang II和collagen I mRNA和蛋白的表达。结果:CHF造模后(第28天),与control组比较,CHF组与AAV9-Jumonji+CHF组MAP和LVEF明显降低(P<0.05);注射AAV9-Jumonji 14 d后(第42天),与control组比较,CHF组MAP和LVEF明显降低(P<0.05),与CHF组比较,AAV9-Jumonji+CHF组MAP和LVEF明显升高(P<0.05);与control组比较,CHF组犬血清中AngⅡ和collagen I含量均升高(P<0.05),ACE2含量降低(P<0.05);与CHF组比较,AAV9-Jumonji+CHF组犬血清中AngⅡ和collagen I含量均降低(P<0.05),ACE2含量升高(P<0.05);与control组比较,CHF组犬心室肌中AngⅡ和collagen I mRNA和蛋白表达均上调(P<0.01),ACE2 mRNA和蛋白表达下调(P<0.01);与CHF组比较,AAV9-Jumonji+CHF组犬心室肌中AngⅡ和collagen I mRNA和蛋白表达均下调(P<0.05),ACE2 mRNA和蛋白表达上调(P<0.05)。结论AAV9-Jumonji抑制慢性心力衰竭犬心脏RAAS活性的增强,从而显著改善慢性心力衰竭犬心功能。

Objective:To observe the effect of AAV9-Jumonji on the activity of heart renin-angiotensin-aldosterone system(RAAS)in chronic heart failure canine,and to explore its mechanism of action in impro-ving chronic heart failure.Methods:The mongrel canine were randomly divided into control group,heart failure(CHF)group,AAV9-Jumonji+heart failure(AAV9-Jumonji+CHF)group;Echocardiography was used to detect the mean artery pressure and Left Ventricular Ejection Fraction;The expression of ACE2,Ang II and collagen I in serum of each group was detected by enzyme-linked immunosorbent assay;The expressions of ACE2,Ang II and collagen I mRNA and protein in ventricular myocytes of canine were detected by qPCR and Western blot.Results:After CHF modeling(Day 28),compared with the control group,MAP and LVEF were significantly lower in the CHF group and the AAV9-Jumonji+CHF group(P<0.05);After 14 days of AAV9-Jumonji injection(day 42),MAP and LVEF were significantly lower in the CHF group compared with the con-trol group(P<0.05),and MAP and LVEF were significantly higher in the AAV9-Jumonji+CHF group com-pared with the CHF group(P<0.05);Compared with the control group,the levels of Ang II and collagen I in the serum of the CHF group were increased(P<0.05),and the ACE2 content was decreased(P<0.05);Compared with CHF group,the levels of Ang II and collagen I in the serum of AAV9-Jumonji+CHF group were decreased(P<0.05),and the content of ACE2 was increased(P<0.05);Compared with the control group,the expression of Ang II and collagen I mRNA and protein in the ventricular myocytes of the CHF group were in-creased(P<0.01),and the expression of ACE2 mRNA and protein was decreased(P<0.01);Compared with the CHF group,the expression of AngII and collagen I mRNA and protein in the ventricular myocytes of the AAV9-Jumonji+CHF group were decreased(P<0.05),and the expression of ACE2 mRNA and protein was in-creased(P<0.05).Conclusions:AAV9-Jumonji inhibited the enhancement of cardiac RAAS activity,and significantly improved cardiac function in canine with chronic heart failure.