血管紧张素转换酶2在心房颤动心房纤维化中的作用

摘要

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 ( TCJF-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, P＜0. 05. ( 3 ) Compared with Sham operation group, the expression of ACE2 mRNA and protein, the expression of Ang1-7 protein were decreased in RAP group, P＜0. 05 ～ 0. 01 respectively, while such decreased expressions were inhibited in Telmisartan group, P＜0. 05 ～ 0. 01 respectively. Conclusion : ACE2 may inhibit atrial fibrosis , and telmisartan could inhibit ACE2 decreasing.%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.