雷米普利对慢性心力衰竭大鼠心肌组织中盐皮质激素受体的影响

目的探讨雷米普利对慢性心力衰竭大鼠心肌组织中盐皮质激素受体(MR)表达及心肌纤维化的影响。方法选择SD大鼠39只,选用慢性心力衰竭造模成功SD大鼠26只,随机分为慢性心力衰竭组(心衰组,13只)、雷米普利治疗组(治疗组,13只),另设假手术大鼠为对照组(13只)。雷米普利治疗4周时,用心肌Masson染色法测定大鼠心肌胶原密度,放射性免疫法测定大鼠心肌组织中血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)含量,实时荧光定量PCR、免疫印迹检测心肌MR表达。结果与对照组比较,心衰组大鼠心肌组织中AngⅡ、ALD显著升高,MR mRNA和蛋白表达显著上调,心肌胶原密度显著增加(P<0.01);与心衰组比较,治疗组大鼠心肌组织中AngⅡ、ALD显著降低.MR mRNA和蛋白表达显著下调,心肌胶原密度显著降低(P<0.01)。结论雷米普利不仅降低慢性心力衰竭大鼠心肌组织中AngⅡ、ALD含量,还可能通过下调心肌MR的表达来抑制心肌纤维化。

The effects of ramipril on mineralocorticoid receptor in myocardium of rats with chronic heart failure

Objective To investigate the effects of ramipril on myocardial mineralocorticoid receptor(MR)in Rats with chronic heart failure(CHF). Methods The rat models of CHF were randomly divided into CHF group (n=13),ramipril treatment group (n=13),and control group (n=13). After treatment for four weeks,the contents of AngⅡ and aldosterone(ALD) in myocardium were determined by radioimmunoassay. The collagen density in myocardium was measured by Masson's Trichrome. The expression of MR was determined by qPCR and Western blot. Results The contents of AngⅡ and ALD in myocardium were increased dramatically in CHF group compared with the control group (P<0.01). The expression of MR mRNA and protein was significantly increased in CHF group. The collagen density in myocardium was also significantly increased in CHF group compared with control group (P<0.01). After treatment with ramipril for four weeeks, the contents of Ang Ⅱ and ALD in the myocardium significantly decreased compared with CHF group (P<0.01). Similarly,the expression of MR mRNA and protein in ramipril group was considerably decreased compared with that in CHF group (P<0.01). At the same time, the collagen density of myocardium was decreased after the treatment with ramipril. Conclusion ACE inhibitors can reduce reactive fibrosis not only by decreasing Ang Ⅱ production but also by attenuating the aldosterone-signaling pathway by decreasing the expression of MR receptors.