心房颤动患者冠状窦血小分子RNA表达差异与价值

目的探讨非瓣膜性心房颤动(房颤)患者冠状窦血小分子RNA(microRNA,miRNA)表达差异及其调控房颤的机制,早期预警诊断和干预的价值。方法选择15例房颤患者作为房颤组,其中阵发性房颤、持续性房颤和永久性房颤各5例,选择健康体检者5例作为正常对照组。导管射频消融术前和术中分别取外周血和冠状窦血,使用miRNA芯片进行全基因组miRNA表达谱微阵列分析,Volcano Plot法获得差异表达miRNA,通过mirbase、miranda、targetscan数据库进行靶基因分析。结果房颤组自身冠状窦血与外周血比较,有14个miRNA表达差异显著,其中6个表达上调:miR-1266、miR-4279、miR-4787-5p、miR-4666a-3p、kshv-miR-K12-6-3p、miR-3150a-5p;8个表达下调:miR-892a、miR-3149、miR-3171、miR-3664-5p、miR-3591-3p、miR-4423-5p、miR-4473、miR-574-3p。miR-1266在阵发性房颤、持续性房颤和永久性房颤患者均明显升高,而miR-3171则显著降低。房颤组冠状窦血和外周血与正常对照组比较,miRNA表达有明显差异(P<0.05)。结论房颤患者冠状窦血更能反映心脏miRNA的代谢与调控状况;外周血miR-3171、miR-892a、miR-3149在房颤发生早期出现,且持续差异表达,有可能成为房颤诊断的标记物;miR-1266、miR-4279、miR-4666a-3p有可能成为未来房颤治疗的干预靶点。

Value of circulating miRNA expression in atrial fibrillation patients

Objective To study the value of circulating miRNA expression in regulation,early diagonosis and treatment of atrial fibrillation(AF).Methods Fifteen AF patients(5with paroxysmal AF,5with persistent AF and 5with permanent AF)served as an AF group and 5subjects undergoing physical examination served as a control group.Peripheral blood(PB)and coronary sinus blood(CSB)samples were taken from the patients before and during radiofrequency ablation.Circulating miRNA expression in whole genome was detected by Volcano Plot and target genes in Mirbase,Miranda and Targetscan were analyzed.Results Of the 14 differently expressed miRNAs in CSB group and PB group,the expressions of 6miRNAs(miR 1266,miR 4279,miR4787-5p,miR 4666a-3p,kshv miR K126-3p and miR3150a-5p)were up-regulated and those of 8miRNAs(miR 892a,miR 3149,miR 3171,miR 3664-5p,miR 3591-3p,miR 4423-5p,miR 4473and miR 574-3p)were down-regulated.The expression level of miR 1266and miRNA was significantly higher and that of miR 3171was significantly lower in AF group than in control group(P<0.05).Conclusion CSB can effectively predict the metabolism and regulation of miRNA in AF patients.The miR 3171,miR 892a,miR 3149are persistently expressed in early AF patients and can thus used as a diagnostic marker of AF.The miR 1266,miR 4279,miR 4666a-3p may serve as AF treatment targets.