慢性心房颤动患者心房肌细胞Kir2.1、Kir3.4和Kv4.3钾通道重构的研究

A Study of Kir2.1, Kir3.4 and Kv4.3 Potassium Channel GeneExpression in Atria of Patients with Chronic Atrial Fibrillation

目的:观察心房颤动(AF)患者心房组织钾通道 IK,ACh、IK1及 Ito1基因水平的改变。方法:将 59 例风湿性心瓣膜病接受心脏外科手术患者分为两组,其中窦性心律(SR)患者 29 例,慢性房颤(CAF)患者 30 例。手术时切取患者右心耳组织,应用RT PCR技术检测心房肌组织 Kir2.1、Kir3.4 和 Kv4.3 mRNA的表达。结果:与 SR组相比,Kir2.1 mRNA的表达在CAF患者中增加明显,达71%(P<0.01),并与 AF时程呈明显正相关(r=0.49,P=0.004)。与之相反的是Kir3.4 mRNA的表达在CAF患者中均显著减少(下降43%,P<0.01),与AF时程呈明显负相关(r=-0.54, P=0.003)。CAF组编码 Ito1的Kv4.3钾通道的mRNA表达较SR组明显下降(下降 60%,P<0.01)。Kv4.3 mRNA表达也与AF时程呈明显负相关(r=-0.67,P=0.003)。结论:慢性房颤患者 Kir2.1的mRNA表达水平增加及Kir3.4和Kv4.3 的mRNA表达水平减少可能分别是 IK1上调、IK,ACh和 Ito1下调的分子基础,而Kir3.4和Kv4.3 mRNA表达水平减少很可能是机体为拮抗AF电重构时有效不应期缩短的代偿机制之一。

Objective: To investigate whether patients with atrial fibrillation show alterations in Kir2.1, Kir3.4 and Kv4.3 potassium channel gene expression. Methods: Right atrial appendages were obtained from 30 patients with chronic atrial fibrillation (CAF) and 29 patients matched as controls in sinus rhythm (SR). All were patients undergoing valve replacement surgery. Total RNA was isolated and reversely transcribed into cDNA. In a semi-quantitative polymerase chain reaction, the cDNA of interest and of GAPDH were coamplified and separated by gel-electrophoresis. Results: Compared with those in SR patients, mRNA levels of Kir2.1 were significant increased in patients with CAF (71%, P<0.01). The mRNA levels of Kir3.4 were obviously reduced in patients with CAF (43%, P<0.01). The mRNA expression of Kv4.3 was significantly decreased in patients with CAF compared with that in patients with SR (60%, P<0.01). A significant correlation was found between the mRNA expression of Kir2.1, Kir3.4, Kv4.3 and AF duration. Conclusion: It suggests that human chronic atrial fibrillation induces transcriptionally mediated upregulation of I K1 and downregulation of I K,ACh and I to1 . Atrial myocytes adapt to atrial fibrillation by downregulating mRNA levels of Kir3.4 and Kv4.3 to counteract the shortening of the atrial effective refractory period due to electrical remodeling.