猪实验性心房颤动模型心房重构及替米沙坦干预的影响

Atrial Fibrillation Caused Atrial Structural Remodeling With the Influence of Telmisartan in Experimental Pigs

目的:观察猪实验性心房颤动时心房结构重构的变化和替米沙坦干预的影响以及血管紧张素转换酶2(ACE2)、胶原蛋白-I的变化。方法:18只猪随机分为正常对照组、快速起搏组和替米沙坦组,每组6只。闭胸法建立猪的持续性心房颤动模型,超声测量实验前、后心室收缩末期左、右心房的面积(LAESA、RAESA)变化;应用程序刺激检测心房颤动的诱发率和持续时间;通过苏木素伊红染色、马松染色和蛋白质印迹法检测ACE2和胶原蛋白-I的变化。结果:与快速起搏组相比,替米沙坦组LAESA、RAESA扩大减轻,心房颤动诱发率降低、持续时间缩短,胶原蛋白-I减少(P<0.05),而ACE2含量明显增加(P<0.05)。RAESA与胶原蛋白-I呈正相关(r=0.956,P<0.01),RAESA与ACE2、ACE2与胶原蛋白-I均呈负相关(r=-0.966,r=-0.948,P<0.01),差异均有统计学意义。结论:猪心房颤动模型心房肌出现结构重构的病理表现,ACE2表达失衡与心房颤动结构重构密切相关;替米沙坦可降低心房颤动的发生率及持续时间,明显改善心房结构重构。

Objective： To study the atrial fibrillation （AF） caused atrial structural remodeling with the influence of telmisartan, and to observe the expression changes of angiotensin converting enzyme-2 （ACE2） and collagen-I in experimental pigs. Methods： AF model was established by rapid right atrial pacing. The experimental pigs were divided into 3 groups and n=6 in each group. Normal control group, the animals received electrode but no pacing, Rapid （right atrial） pacing group, and Telmisartan group, the animals received rapid pacing plus telmisartan 60 mg/（kg. d）. Left and right atrial end-systolic areas （LAESA and RAESA） were measured by echocardiography before and after the experiment, the AF rate and duration were detected by electrophysiological stimulation. All animals were treated for 2 weeks. The expressions of ACE2 and collagen-I were examined by HE staining, Masson staining and Western Blot analysis. Results： Compared with Rapid pacing group, Telmisartan group presented reduced enlargement of LAESA and RAESA, decreased AF rate and duration, decreased collagen-I, P〈0.05, while increased ACE2, P〈0.05. RAESA was positively related to collagen-I （r=0.956, P〈0.01）, RAESE was negatively related to ACE2 （r=-0.966, P〈0.01）, ACE2 was negatively related to collagen-I （r=-0.948, P〈0.01）. Conclusion： AF may cause atrial structural remodeling in experimental pig model; it was closely related to imbalance of ACE2 expression. Telmisartan could reduce AF occurrence rate and duration, and obviously improve atrial structural remodeling.