特异性阻断Kv1.5通道对心房颤动患者缝隙连接蛋白40表达的影响

Effect of the protein expressions of gap junction Cx40 by using Ibutilide to selective act on Kv1. 5 potassium channel on atrial fibrillation patients

目的利用伊布利特特异性阻断超速延迟整流性钾通道(Kv1.5)后对缝隙连接蛋白(Cx)40表达的影响,探讨Kv1.5通道可能是心房肌缝隙连接蛋白下游信号传导通路之一,揭示心房颤动(AF)的可能发生机制。方法实验标本取自风湿性心脏病接受心脏瓣膜置换手术患者的右心耳组织,根据患者术前心律将标本分为2组:风湿性心脏病[窦性心律组(SR组)]和风湿性心脏病合并AF组(AF组)。采用酶解法分离风湿性心脏病接受手术患者心房肌细胞、培养心房肌细胞和运用Western blot技术检测两组心房肌细胞运用伊布利特特异性阻断Kv1.5通道前后Cx40的表达情况。结果利用伊布利特特异性阻断Kv1.5通道后,AF组患者心房心肌细胞Cx40的表达水平较阻断前明显增加(P<0.01);而在SR组中,阻断前后Cx40/GAPDH比值的变化不明显。结论 Kv1.5通道的开放状态可能会影响Cx40的表达,从而揭示AF的发生机制中电重构可能会引起结构重构。

Objective To evaluate the expression of atrial muscle gap junction Cx40 in rheumatic heart disease with chronic atrial fibrillation by using the new class Ⅲantiarrhythmie drug ibutilide specific block ultra-rapid delayed rectifier potassium channels（ Kv1.5 ） , to discuss possibility of the Kv1.5 potassium channels to be one of downstream signal transduetion pathways of the atrial muscle gap junction protein,and to reveal the possible mechanism of atrial fibrillation （AF）. Methods The experiment specimens were taken from right atrial appendage tissues of rheumatic heart disease patients who accepted the valve replacement surgeries, and these specimens were divided into 2 groups according to the heart rate before surgeries. The sinus rhythm group of rheumatic heart disease [ sinus rhythm （SR） group ], and the atrial fibrillation group of rheumatic heart disease heart disease （ AF group）. Enzyme was used to dissociate atrial myocytes, atrial myocytes was cultured and Western blot was used to detect the protein expressions of Cx40 in two groups before and after they were selective acted on by the selective Kv1.5 potassium channel blocker-ibutilide. Results After using the Class Ⅲ antiarrhythmic agents to selective act on Kv1.5 potassium channel in rheumatic heart disease with chronic atrial fibrillation, the expression of Cx40 was significantly higher in AF group （P 〈 0.01 ）. The protein expression of Kv1.5 was not significantly changed in SR group. Conclusion In the group of rheumatic heart disease with atrial fibrillation, the expression of Cx40 was significantly increased after using the specific inhibitor of Kv1.5 potassium channel blocker in AF group,proving that the open Kv1.5 potassium channels may affect the expression of connexin Cx40, which further reveals that electrical remodeling may lead to the diversification of structural remodeling in AF.