血管紧张素转换酶2在心房颤动心房纤维化中的作用

Involvement of Angiotensin Converting Enzyme2 on Atrial Fibrosis in Pigs With Experimental Atrial Fibrillation

目的:探讨血管紧张素转换酶2(ACE2)在心房颤动心房纤维化中的作用及替米沙坦对ACE2的影响。方法:18只健康小家猪随机分为3组,分别为假手术组、快速起搏组、替米沙坦组,每组6只。替米沙坦组于心房起搏前3天至起搏期间喂服替米沙坦1.5 mg/(kg.d)。2周后处死所有实验猪,开胸取左心房心肌,马松三色染色检测胶原沉积;蛋白质印迹和逆转录聚合酶链式反应分别检测转化生长因子-β1(TGF-β1)、ACE2的蛋白和信使核糖核酸(mRNA)表达;酶联免疫吸附法检测血管紧张素1-7的表达。结果:①马松三色染色:与假手术组比快速起搏组胶原阳性染色增多;替米沙坦组较快速起搏组减少。②与假手术组比快速起搏组TGF-β1的蛋白表达和mRNA表达均增加(P<0.05);应用替米沙坦后可减轻它们的增加(P<0.05),差异均有统计学意义。③与假手术组比快速起搏组ACE2的蛋白表达和mRNA表达及血管紧张素1-7的蛋白表达均降低(P<0.05～0.01);应用替米沙坦后可抑制ACE2的蛋白表达和mRNA表达及血管紧张素1-7的蛋白表达下降(P<0.05～0.01),差异均有统计学意义。结论:ACE2可能通过促进血管紧张素1-7合成、下调TGF-β1来抑制慢性心房颤动的心房纤维化,替米沙坦可提高慢性心房颤动心房ACE2的表达。

Objective： To study the involvement of angiotensin converting enzyme2（ACE2） on atrial fibrosis in pigs with experimental atrial fibrillation and the effect of telmisartan on ACE2. Methods： The pig model of atrial fibrillation was established by rapid right atrial pacing.18 healthy pigs were randomly divided into 3 groups,n=6 in each group.Sham operation group,in which the pace makers were implanted but not used.Rapid atrial pacing（RAP） group and Telmisartan group,in which the animals were treated with Telmisartan 1.5 mg/kg/d from 3 days before until 2 weeks after the operation.All the pigs were sacrificed after 2 weeks treatment.The deposition of cardiac collagen tissue was observed by Masson trichrome staining,the mRNA and protein expression of ACE2 and transforming growth factor（TGF-β1） in left atrium were analyzed by RT-PCR and Western blot,the angiotensin（Ang） 1-7 levels were measured by ELISA. Results：（1） Compared with Sham operation group,Masson trichlome staining indicated significantly increased interstitial fibrosis in RAP group but no obvious changes in Telmisartan group.（2） Compared with Sham operation group,the mRNA and protein expression of TGF-β1 significantly increased in RAP group,such expression in Telmisartan group was much lower than that in RAP group,P0.05.（3） Compared with Sham operation group,the expression of ACE2 mRNA and protein,the expre-ssion of Ang1-7 protein were decreased in RAP group,P0.05~0.01 respectively,while such decreased expressions were inhibited in Telmisartan group,P0.05~0.01 respectively. Conclusion： ACE2 may inhibit atrial fibrosis,and telmisartan could inhibit ACE2 decreasing.