快速心房起搏兔肺静脉心肌袖细胞膜钾通道基因表达及胺碘酮的影响

Potassium channel gene expression in myocardial sleeves of pulmonary vein and effects of amiodarone on rabbits with rapid atrial pacing

目的:观察快速心房起搏对兔肺静脉心肌袖细胞膜钾通道及其亚型(Kv4.3、Kir6.2)基因表达的影响及胺碘酮的干预作用。方法:新西兰兔30只,随机分为3组(n=10),Ⅰ组:对照组;Ⅱ组:快速心房起搏组;Ⅲ组:心房快速起搏+胺碘酮组。3组均经颈内静脉将电极置入右心房,其中Ⅰ组不予心房起搏,Ⅱ组和Ⅲ组以600 beats/min连续起搏右心房7 d;同时Ⅲ组按100 mg.kg-1.d-1给予胺碘酮灌胃,Ⅰ组和Ⅱ组则给予等量无药物成分的糖片(安慰剂)7 d。剪取3组兔的肺静脉心肌袖组织,应用逆转录-聚合酶链反应技术(RT-PCR)以3-磷酸甘油醛脱氢酶(GAPDH)为内参照,测定肺静脉心肌袖细胞Kv4.3、Kir6.2的mRNA表达水平。结果:Ⅱ组Kv4.3钾通道mRNA表达低于Ⅰ组45%(P<0.01),Ⅲ组低于Ⅰ组73%(P<0.01),Ⅲ组低于Ⅱ组51%(P<0.01),Kir6.2mRNA的表达Ⅱ组比Ⅰ组高32%(P<0.01),Ⅲ组与Ⅰ组无明显差异(P>0.05),Ⅲ组低于Ⅱ组22%(P<0.05)。结论:快速心房起搏可引起兔肺静脉心肌袖细胞钾通道基因表达变化,后者可能是肺静脉心肌袖接受电刺激后钾离子通道重构的分子基础,肺静脉心肌袖钾通道可能是胺碘酮的作用靶点之一。

AIM ： To investigate the potassium channel gene expression of myocardial sleeves of pulmonary vein and effects of amiodarone on rabbits with rapid atrial pacing. METHODS ： Rabbits were divided into three groups （ n = 10）, （1） the control group with sham operation and placebo; （2） the right atrial pacing （RAP） group at 600 beats/min with the placebo; （3） the anliodarone group treated for seven days with oral amiodarone at 100 mg·kg^-1·d^-1. Based on RAP simultaneously, the messenger ribonucleic acid （mRNA） of specimen was measured by reverse transcription - polymerase chain reaction. RESULTS ： Compared with the control group, Kv4. 3 （ transient outward K ^＋ current, Itol ） mRNA expression in RAP group was reduced by 51% （P 〈 0. 01 ） following seven days of RAP, and that in the amiodarone group was reduced by 45% （P 〈0. 01 ） compared with the RAP group. The Kit6. 2 （inward rectifier inhibited by ATP, IKATP ） channel gene expression was upregulated by 32% in RAP group（P 〈0. 01 ） than that in control group whereas the Kit6. 2 channel gene expression in amiodarone group downregulated by 22% （ P 〈 0.05 ） than that in RAP group. CONCLUSION ： The rapid atrial pacing can result in changes of the potassium channel gene expression in myocardial sleeves of pulmonary vein, which might be the molecular basis of the potassium channel remodeling and one of targets of amiodarone used for antiarrhythmias.