【摘要】：研究目的:為了探討房顫患者重要離子通道蛋白的mRNA組學改變及意義,為揭示房顫電重構的機制和干預奠定基礎。研究方法:選擇2012年1月至2015年1月北京世紀壇醫(yī)院90例行房顫射頻消融術患者(陣發(fā)性、持續(xù)性和永久性房顫各30例),90例健康體檢者作為正常對照組,房顫射頻消融術中分別取冠狀竇血和外周靜脈血,使用mRNA芯片進行全基因組mRNA表達譜微陣列分析,Real-time PCR對血液主要離子通道基因mRNA表達差異結果進行驗證。研究結果:房顫患者與正常對照組外周血全基因組mRNA表達比較,553種mRNA表達上調,1018種表達下調(P0.05)。離子通道蛋白12種mRNA表達升高≥2.0倍,10種表達下降≥2.0倍。其中,K+通道基因KCNE4,KCND2,KCNN4明顯下降,KCNA5下降11.54倍(P0.00001);KCNS3,KCNS1,KCNG1,KCNG7,以及Ca++通道基因CACNA2D3明顯升高,而If通道HCN3基因及GJA9縫隙連接蛋白mRNA表達也明顯下調�；颊吖跔罡]血與自身外周血mRNA比較,12種離子通道蛋白mRNA表達差異≥2.0倍;與對照組外周血比較,7種離子通道蛋白mRNA表達差異≥2.0倍,其中KCNA5基因表達下調8.13倍。研究結論:房顫患者IKur通道KCNA5基因表達下調最為明顯,更多的鉀離子通道表達差異較為顯著,所以鉀離子通道重構可能在房顫電重構中起著主導或更為重要的作用。其它涉及神經(jīng)內分泌調節(jié)、興奮收縮偶聯(lián)和基因表達等的離子通道與房顫的關系有待深入研究。
[Abstract]:Objective: to investigate the mRNA changes of important ion channel proteins in patients with atrial fibrillation, and to lay a foundation for revealing the mechanism and intervention of atrial fibrillation electrical remodeling. Methods: from January 2012 to January 2015, 90 patients underwent radiofrequency ablation of atrial fibrillation (30 patients with paroxysmal, 30 patients with persistent atrial fibrillation and 30 patients with permanent atrial fibrillation) and 90 healthy people as control group. The coronary sinus blood and peripheral venous blood were taken from radiofrequency ablation of atrial fibrillation respectively. The microarray analysis of the whole genome mRNA expression profile was performed using mRNA microarray. The results of mRNA expression of the main ion channel genes in the blood were verified by Real-time PCR. Results: compared with the control group, 553 kinds of mRNA were up-regulated and 1018 were down-regulated (P0.05). The expression of 12 kinds of ionic channel protein (mRNA) was more than 2.0 times higher than that of 10 species. K channel gene KCNE4,KCND2,KCNN4 and KCNA5 decreased 11.54 times (P0.00001), KCNS3,KCNS1,KCNG1,KCNG7, and Ca channel gene CACNA2D3 increased, and If channel HCN3 gene and GJA9 gap junction protein mRNA expression decreased significantly. The expression of 12 ion channel proteins (mRNA) in coronary sinus blood was more than 2.0-fold higher than that in peripheral blood. Compared with the peripheral blood of the control group, the mRNA expression of the seven ion channel proteins was more than 2.0 fold, and the expression of KCNA5 gene was decreased by 8.13 times. Conclusion: the down-regulation of IKur channel KCNA5 gene expression is most obvious in patients with atrial fibrillation, and the difference of potassium channel expression is more significant. Therefore, potassium channel remodeling may play a leading or more important role in atrial fibrillation electrical remodeling. The relationship between atrial fibrillation and other ion channels involved in neuroendocrine regulation, excitatory and contractile coupling and gene expression needs further study.
【學位授予單位】：首都醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R541.75

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1 王伊然;崔m鏘，

本文編號：2368863