摘要
目的探讨房颤射频消融手术对房颤离子通道蛋白和离子流重构的影响和调控作用，寻找可能的miRNAs调控干预靶点，为房颤的预警干预奠定基础。方法选择30例行房颤射频消融术患者（阵发性、持续性和永久性房颤各10例），健康体检者10名作为正常对照组。射频消融术前和术后3个月分别取外周血，使用miRNA芯片进行全基因组miRNA表达谱微阵列分析，Real—timePCR对调控离子通道蛋白的主要miRNAs表达差异结果进行验证，通过mirbase、miranda、targetscan数据库进行靶基因分析。结果主要参与调控离子通道蛋白SCN5A、CACNAlC、KCNA5、KCNH2、KCNEI、KCNQl、KCNJ2、KCNC4、KCND3、KC—NN3、HCNl、HCN3和HCN4的miRNAs共21个。射频消融术前房颤组与正常对照组比较，其表达有显著差异（P〈0．05）。术后3个月房颤组与自身术前比较，这些miRNAs表达亦有明显差异（P〈0．05），其中miR-1266等5个miRNAs术前表达上凋，术后明显下调，仅miR-3664—5p术后较术前进一步下调，其余15种miRNAs均术前表达下调，术后显著上调。调控外向型钾离子通道（如KCNA5）的miRNA手术前后调控趋势一致，调控幅度较大。结论外向性K＋离子流增多在房颤电重构中可能起主要作用。房颤射频消融手术对房颤的电重构起到了离子流再平衡和逆重构的作用。调控多个离子流的miR-1266等miRNAs，有可能成为未来房颤干预的靶点。
Objective To study the effect of radiofrequency ablation （RFA） on atrial electrical remodel- ing, ion flow rebalancing and reverse remodeling, and try to find possible target miRNAs which can guide early diagnosis and intervention of atrial fibrillation（AF）. Methods The Peripheral blood（PB） were taken from 30 AF patients in AF group before and ＇after RFA 3 months, in which included patients with 10 paroxysmal, 10 persistent and lO permanent AF, and 10 healthy subjects in control group. The circulating miRNAs expression profile differ- ence in whole genome was detected with the microRNA chips （microRNA v 18.0）, analyzed with Volcano Plot and tMEV software respectively, and further validated by Real-time PCR. Furthermore, the target gene of miRNAs was predicted through the Mirbase, Miranda and Targetscan databases. Results The miRNAs expressions profile Be- fore RFA were significantly different in AF group compared with conunl group （P〈0.05）, and also tremendously different compared with which of the patients themselves before and after RFA of 3 months. The main 21 miRNAs regulating ion channel protein including SCN5A,CACNA1C,KCNA5, KCNH2, KCNE1,KCNQ1,KCNJ2, KCNC4, KCND3,KCNN3,HCN1,HCN3 and HCN4, there were 5 ones which was up-regulation before RFA, but down- regulation after RFA of 3 months including miR-1266 etc. Oppositely, others were down-regulation before RFA,while up-regulation after RFA of 3 months significantly excluding only miR-3664-5p down-regulated 8.88 times before RFA, and further down-regulated 46.06 times after RFA 3 months. Especially, miRNAs regulating Out- flowing K＋ ion channel protein, such as KCNA5, was that the regulating tendency was unanimous, and adjusting amplitude was larger before and thereafter RFA. Conclusion Out-flowing K＋ ion current increasing may play a leading role in atrial electrical remodeling. RFA can change the expressions of miRNAs regulating the ion channel proteins, rebalanee and reverse the ion current remodeling of AF. miRNAs which can simultaneously regulate multi- ple ion channels, such as miR-1266 etc., may become the future targets for AF intervention.
出处
《中国心血管病研究》
CAS
2015年第12期1090-1096,1151,1152,共9页
Chinese Journal of Cardiovascular Research
关键词
心房颤动
射频消融
微小RNA
离子通道
基因调控
组学研究
Atrial fibrillation
Radiofrequency ablation
miRNA
Ion channel
Gene regulation
Genomics research
作者简介
通讯作者：杨水祥，E-mailsxyang68@163．com
