心房颤动犬心房肌细胞骨架重构及贝那普利的干预作用

目的 观察快速心房起搏心房颤动(房颤)犬心房肌细胞骨架重构及贝那普利的干预作用.方法 采用慢件快速左心房起搏建立房颤犬模型,分为假手术组(6只)、房颤组(7只)、干预组(6只).房颤组应用固定频率型起搏器,600次/min起搏6周;干预组于起搏前1周开始每日服贝那普利(1 mg/kg).实验结束时取材,HE染色测定心房肌细胞直径;Masson染色进行心房肌纤维化定量分析;免疫组织化学法检测结蛋白心脏原位蛋白分布及表达;RT-PCR方法测定心房肌组织β-微管蛋白、结蛋白mRNA表达水平.结果 假手术组、房颤组、干预组左心房肌细胞直径分别为(19.6 ±2.9)μm、(27.9 ±3.8)μm、(25.1 ±3.4)μm,右心房分别为(18.7 ±2.6)μm、(26.8 ±3.2)μm、(25.2 ±3.5)μm,房颤组、干预组左、右心房肌细胞直径均明显长于假手术组(均P＜0.01);左心房胶原容积分数(CVF)分别为(9.2±0.9)%、(16.9 ±1.1)%、(11.3 ±0.8)%,右心房CVF分别为(9.3±0.8)%、(15.7 ±2.3)%、(10.9 ±0.8)%,房颤组左、右心房CVF均高于假手术组(均P＜0.01),干预组均明显低于房颤组(均P＜O.01).免疫组化示房颤组结蛋自在细胞质内表达增多,而闰盘处表达不明显,房颤组左、右心房肌结蛋白吸光度值均高于假手术组(均P＜0.01),干预组均明显低于房颤组(均P＜0.01).房颤组左、右心房肌结蛋白、微管蛋白mRNA表达均高于假手术组(均P＜0.01);干预组房颤组(均P＜0.01).结论 快速心房起搏房颤犬心房肌细胞骨架发生重构且贝那普利对其有干预作用.

Effect of benazepril on atrial cytoskeleton remodeling in the canine atrial fibrillation models

Objective To investigate the effect of benazepril on atrial cytoskeleton remodeling in atrial fibrillation(AF)canines induced by chronic rapid atrial pacing(RAP). Methods Twenty canines were randomly divided into 3 groups: (1)Sham-operated group without RAP; (2)AF group: AF established by RAP at 600 beats per minute for 6 weeks; (3)Benazepril group: benazepril was dosed from 1 week pre-pacing to 6 weeks post-pacing. The diameter of atrial cardiomyocyte was measured, collagen volume fraction(CVF)analyzed by Masson staining and the expression and distribution of desmin were assayed by immunohistochemistry. RT-PCR method was used to semi-quantify the mRNA expression of β-tubulin and desmin. Results The diameter of atrial eardiomyocyte increasod in AF group LA: (27.9±3.8)μm; RA: (26.8±3.2)μm]and benazepril groupLA: (25.1 ±3.4)μm; RA: (25.2±3.5)μm]than sham-operated groupLA: (19.6±2.9)μm; RA: (18.7 ±2.6)μm](P＜0.01). CVF increased in AF group than sham-operated groupLA: (16.9±1.1)%vs(9.2 ±0.9)%, RA: (15.7±2.3)%vs(9.3±0.8)%, P＜0.01)and it decreased in benazepril group than AF groupLA: (11.3±0.8)%vs(16.9 ±1.1)%, RA: (10.9±0.8)%vs(15.7±2.3)%, P＜0.01). Normal desmin cross-striations were lost in atrial cardiomyocyte and the desmin organization became irregular in AF group. The A values analyzed by immunohistochemistry of desmin increased in AF group than sham-operated group and they decreased in benazepril group than AF group(P＜0.01). The expression of mRNA level of desmin and β-tubulin were up-regulated in AF group than sham-operated group, (LA: 1.0 ±0.3 vs 0.6 ±0.3, 0.9 ±0.4 vs 0.6 ±0.3; RA: 1.0±0.6 vs 0.6±0.2, 1.1 ±0.3 vs 0.7 ±0.4, P＜0.01) and they were down-regulated in benazepril group than AF group(LA: 0.8 ±0.4 vs 1.0±0.3, 0.7±0.3 vs 0.9±0.4; RA: 0.7±0.3 vs1.0±0.6, 0.7±0.3 vs 1.1±0.3, P＜0.01). Conclusion Benazepril Can favorably improve atrial cytoskeleton remodeling in the canine atrial fibrillation model.