房颤患者离子通道蛋白基因mRNA组学改变及其意义
发布时间：2018-12-08 19:18
【摘要】：研究目的:为了探讨房颤患者重要离子通道蛋白的mRNA组学改变及意义,为揭示房颤电重构的机制和干预奠定基础。研究方法:选择2012年1月至2015年1月北京世纪坛医院90例行房颤射频消融术患者(阵发性、持续性和永久性房颤各30例),90例健康体检者作为正常对照组,房颤射频消融术中分别取冠状窦血和外周静脉血,使用mRNA芯片进行全基因组mRNA表达谱微阵列分析,Real-time PCR对血液主要离子通道基因mRNA表达差异结果进行验证。研究结果:房颤患者与正常对照组外周血全基因组mRNA表达比较,553种mRNA表达上调,1018种表达下调(P0.05)。离子通道蛋白12种mRNA表达升高≥2.0倍,10种表达下降≥2.0倍。其中,K+通道基因KCNE4,KCND2,KCNN4明显下降,KCNA5下降11.54倍(P0.00001);KCNS3,KCNS1,KCNG1,KCNG7,以及Ca++通道基因CACNA2D3明显升高,而If通道HCN3基因及GJA9缝隙连接蛋白mRNA表达也明显下调。患者冠状窦血与自身外周血mRNA比较,12种离子通道蛋白mRNA表达差异≥2.0倍;与对照组外周血比较,7种离子通道蛋白mRNA表达差异≥2.0倍,其中KCNA5基因表达下调8.13倍。研究结论:房颤患者IKur通道KCNA5基因表达下调最为明显,更多的钾离子通道表达差异较为显著,所以钾离子通道重构可能在房颤电重构中起着主导或更为重要的作用。其它涉及神经内分泌调节、兴奋收缩偶联和基因表达等的离子通道与房颤的关系有待深入研究。
[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.
【学位授予单位】：首都医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.75
[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.
【学位授予单位】：首都医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.75
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