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目的观察西拉普利和缬沙坦对长期心房快速起搏诱发心房颤动犬心房结构和功能重构的影响,并探讨其机制。方法2006年3月至10月在哈尔滨医科大学第一临床医学院动物实验中心,将实验犬随机分为假手术组(n=6)、对照组(n=7)、西拉普利组(n=7)和缬沙坦组(n=7)。对照组、西拉普利组和缬沙坦组犬心房快速起搏6周,建立心房颤动(AF)犬模型。西拉普利组和缬沙坦组犬分别于起搏前1周开始每天服用西拉普利(1mg/kg)和缬沙坦(30mg/kg),直至起搏结束。分别于起搏前、起搏6周后,超声测定左心房和左心耳结构和功能变化;Masson染色检测各组犬心房肌胶原容积分数(CVF)改变;免疫组化法测定心房肌细胞外信号调节激酶ERK1和ERK2表达情况;末端脱氧核糖核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL法)检测心房肌细胞凋亡情况。结果(1)起搏6周后,西拉普利组和缬沙坦组犬较对照组犬左心房最大及最小容积、左心耳最大及最小容积明显缩小,左心房和左心耳射血分数、左心耳最大正向和负向血流速度显著增大。(2)与对照组犬相比,西拉普利组和缬沙坦组AF犬心房肌ERK1、ERK2表达和CVF值明显降低。结论西拉普利和缬沙坦能够阻止长期心房快速起搏诱发AF犬心房肌纤维化及细胞凋亡,防止AF犬心房结构重构和功能降低。
Objective To observe the effects of cilazapril and valsartan on atrial fibrillation in atrial fibrillation dogs with chronic atrial fibrillation and functional remodeling, and to explore its mechanism. Methods From March 2006 to October 2006, experimental dogs were randomly divided into sham operation group (n = 6), control group (n = 7), cilazapril group (n = n = 7) and valsartan (n = 7). The canine model of atrial fibrillation (AF) was established by rapid atrial pacing in control, cilazapril and valsartan dogs for 6 weeks. Cilazapril and valsartan groups were given Cilazapril (1 mg / kg) and valsartan (30 mg / kg) every day one week prior to pacing until pacing ended. The changes of structure and function of left atrium and left atrial appendage were measured before pacing and 6 weeks after pacing. Masson staining was used to detect changes of atrial collagen volume fraction (CVF) in each group. Atrial extracellular signal Regulated the expression of ERK1 and ERK2, and detected the apoptosis of atrial myocytes by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL). Results (1) After 6 weeks of pacing, the maximum and minimum volume of left atrium and the maximum and minimum volume of left atrial appendage in civets and valsartan groups were significantly reduced. The left atrium and left atrial appendage ejection fraction, Left atrial appendage maximum positive and negative flow velocity increased significantly. (2) Compared with control dogs, the expressions of ERK1, ERK2 and CVF in atrial fibrillation of civets in Cilazapril and valsartan groups were significantly decreased. Conclusion Cilazapril and valsartan can prevent long-term atrial pacing induced atrial fibrillation and apoptosis in dogs and can prevent atrial structural remodeling and dysfunction in AF dogs.