风湿性心脏瓣膜病合并房颤中异常钾离子通道的实验研究

An experimental study on abnormal potassium channels in rheumatic heart disease complicated with atrial fibrillation

目的探讨心脏瓣膜病合并房颤患者心房组织中异常活动钾离子通道的类型及功能。方法对2015年8月—2016年7月蚌埠医学院第一附属医院心脏外科32例二尖瓣和／或主动脉瓣置换术患者资料进行回顾性分析。其中，男14例、女18例，年龄48～71岁；房颤患者19例，窦性心律患者13例。在体外循环开始前，常规取房颤患者的左右心房组织及窦性心律患者的右心房组织，置于液氮中备用。通过转录组学及逆转录-PCR方法，对比房颤患者的左右心房组织与窦性心律患者的右心房组织中钾离子通道表达，分析与房颤发生相关的特异性钾离子通道。结果转录组学分析发现在房颤组中，钾离子通道在生物过程、细胞成分及分子功能上差异均有统计学意义（P值均〈0．01）；钾离子通道KCNMB1在房颤组内的左、右房间的表达差异无统计学意义（0．24±0．02VS0．28±0．04，P〉0．05），KCNH7（0．29±0．03vs0．45±0．06，P〈0．05）、KCNH2（0．24±0．04VS0．79±0．1，P〈0．01）、KCNJ4（0．1±0．02vs0．75±0．1，P〈0．01）、KCNA6（0．33±0．03vs0．89±0．05，P〈0．01）、KCNK5（0．21±0．04vs0．94±0．04，P〈0．01）和KCNN2（0．35±0．06vs0．58±0．1，P〈0．05）差异均有统计学意义。结论在心脏瓣膜病合并房颤患者中，多种钾离子通道功能异常，其中KCNH7、KCNH2、KCNJ4、KCNA6、KCNK5及KCNN2与房颤的发展有关。

Objective To study the types and functions of potassium channels in rheumatic heart disease （RHD） complicated with atrial fibrillation （AF）. Methods Data of nineteen patients with AF and 13 patients with sinus rhythm were analyzed. By transcriptome and RT-PCR, specific expression of potassium channels was observed. Results Besides diameter of left atrium, the clinical characteristic were matched. The function of potassium channels related to biological process, cellular component and molecular function were significantly different （ all P values 〈 0.01 ）. KCNH7 （0.29 ±0.03 vs 0.45 ± 0.06, P 〈 0. 05）, KCNH2（0.24 ±0.04 vs 0.79 ±0.1, P〈0.01）, KCNJ4（0. 1 ±0.02 vs 0.75 ±0.1, P〈0.01）, KCNA6（0.33±0.03 vs 0.89 ±0.05, P 〈0.01）, KCNK5（0.21 ±0.04 vs 0.94 ±0.04, P 〈0.01） and KCNN2（0.35 ±0.06 vs 0.58 ±0.1, P 〈0.05） were down-regulated in left atrium tissue from AF patients. Conclusions Functions of potassium channels are changed in RHD with AF patients, KCNH7, KCNH2, KCNJ4, KCNA6, KCNK5 and KCNN2 are associated with the development of AF.