持续性心房颤动患者2型小电导钙激活钾通道基因和蛋白表达的变化

Changes in gene and protein expression of type 2 small-conductance calcium-activated potassium channel in patients with persistent atrial fibrillation

目的探究人患持续性心房颤动(房颤)后2型小电导钙激活钾通道(type 2small-conductance calcium-activatedpotassium channel,SK2)的变化在电重构中的作用。方法选择风湿性心脏病行二尖瓣置换成形术的患者,持续性房颤23例(房颤组,其中3例合并陈旧脑栓塞),窦性心律18例(窦律组)。体外循环前取新鲜右心耳组织,通过免疫组化和逆转录酶联聚合反应(reverse transcription polymerase chain reaction,PT-PCR)方法,测定SK2基因和蛋白表达的差异。结果基线资料:与窦律组比较,房颤组患者二尖瓣狭窄病变更多,左房内径和心胸比率更大,差异有统计学意义(P<0.05),其他相关指标无明显差异(P>0.05)。PT-PCR:窦律组和房颤组的KCNN2(SK2的编码基因)/GAPDH(内参基因)比值分别为1.25±0.52和0.70±0.30(P<0.05),SK2基因表达下调44%。免疫组化:与窦律组比较,房颤组心房肌细胞增大明显,SK2蛋白表达下调13%,但差异无统计学意义(P>0.05),SK2通道蛋白在细胞内分布2组差别无统计学意义。结论与初步动物实验结果不同,人患持续性房颤后SK2基因和蛋白表达下调,用于防治动物房颤有效的SK2特异性阻断剂能否用于罹患持续性房颤的患者有待进一步研究。

Objective To explore the role of changes of SK2in electrical remodeling after patients suffering from persistent atrial fibrillation（AF）.Methods Total 41patients with rheumatic heart disease accepted mitral valve replacement arthroplasty,23patients with persistent AF（AF group,3cases had suffered cerebral embolism previously）and 18patients with sinus rhythm（SN group）.Before cardiopulmonary bypass,part of right atrial appendages were taken freshly for the determination SK2gene and protein expression differences in the two groups by immunohistochemistry and reverse transcription polymerase chain reaction（PT-PCR）method.Results Baseline information：Compared with SN group,patients in AF group had more mitral stenosis,larger atrial diameters and cardiothoracic ratio with statistical significance（P0.05）,which showed no significant differences in other aspects（P0.05）.PT-PCR：KCNN2（SK2encoding gene）/GAPDH（internal reference gene）ratio in SN and AF group was 1.25±0.52and 0.70±0.30,respectively（P0.05）,and SK2gene expression in AF group decreased 44%.Immunohistochemistry：Compared with SN group,atrial myocytes in AF group was significantly increased,SK2 protein expression decreased 13%,but did not have statistical significance（P0.05）,SK2channel protein distribution in the cell had no significant difference between the two groups.Conclusion Inconsistent with preliminary results of animal experiments,people with persistent AF has decreased SK2gene and protein expression and further study can be done to conform whether specific SK2inhibitors,which are effective to prevent and treat atrial fibrillation in animals,are appropriate for patients suffering from persistent AF.