依那普利和厄贝沙坦及血管紧张素(1-7)对快速心房起搏犬心房肌钠通道基因表达的影响

Effects of enalapril,irbesartan and Ang-(1-7) on atrial sodium channel gene expression in a canine model of rapid atrial pacing

目的观察依那普利、厄贝沙坦和血管紧张素(1-7)[Ang-(1-7)]对快速心房起搏犬心房肌细胞钠通道(Nav1.5)基因表达的干预作用。方法普通杂种犬30只,随机分为5组,每组6只。心房起搏组、依那普利组、厄贝沙坦组和Ang(1-7)组犬行快速心房起搏(500/min)2周;假手术组犬不行起搏刺激,普通饲养2周。应用RT-PCR检测各干预因素对Nav1.5α亚单位基因表达的影响。结果与假手术组比较,心房起搏组犬Nav1.5α亚单位mRNA表达明显降低(P<0.05);依那普利组、厄贝沙坦组犬可逆转快速心房起搏所致的Nαv1.5α亚单位mRNA表达水平的降低(P<0.05);Ang-(1-7)组犬Nav1.5α亚单位mRNA表达水平无明显改变(P>0.05)。结论快速心房起搏可降低犬心房肌Nav1.5α亚单位mRNA表达,依那普利、厄贝沙坦可逆转快速起搏所致的Nav1.5α亚单位mRNA表达的降低,Ang(1-7)则无明显影响。

Objective To observe the effects of enalapril,irbesartan and Ang-（1-7） on atrial sodium channel（Nay1.5 a） subunit mRNA expression induced by rapid atrial pacing in the canine model of AF. Methods Thirty mongrel dogs of either sex were randomly assigned to the sham-opera-ted,paced,enalapril,irbesartan or Ang-（1-7） group of 6 dogs each. A programmable pacemaker pacing at 500 beats per minute was inserted in a subcutaneous pocket, and an atrial pacing lead was positioned in the right atrium. In the paced,enalapril,irbesartan and Ang-（1-7） groups,rapid pacing was maintained for 2 weeks. The sham-operated dogs underwent pacemakers and electrodes insertion, but the pacemakers were not activated to provide atrial pacing. At the end of the experi- ments,RT-PCR was used to assess possible changes in cardiac gene expression of Nay1.5 ~ sub- unit in atrial tissue. Results Compared with the sham-operated dogs, Navl. 5 a subunit mRNA expression decreased dramatically in the dogs of paced group after 14 days of rapid atrial pacing （P〈i 0.05）. Enalapril and irbesartan prevented the decrease in Nay1.5 αsubunit mRNA expression （P 〈 0.05）. Ang-（1-7） had no effects on the decrease （P〉0.05）. Conclusions Rapid pacing downregulated the Nay1.5 α sulbunit gene expression. Enalapril and irbesartan significantly up-regulated the expression of gene Nay1.5,while Ang-（1-7） did not show similar effects on it.