研究表明miRNA-215和miRNA-199可能参与心房颤动（房颤）的发生，但机制尚不明确。我们前期的工作提示心房Cx40重构与房颤发生密切相关。Nkx2.5(Cx40转录因子)和Cx40基因分别是miRNA-215、miRNA-199潜在靶基因。据此，我们假说，各种病因导致的miRNA-215、miRNA-199上调，在转录及转录后水平下调Cx40，参与房颤的发生。我们将利用PCR、免疫荧光、Western-blot、双荧光素酶报告基因和基因干预等方法，检测房颤患者和房颤犬心房miRNA-215、miRNA-199、Nkx2.5及Cx40表达变化；构建miRNA-215、miRNA-199过/低表达心房肌细胞和小鼠模型，观察对Nkx2.5、Cx40表达和房颤易感性的影响，探讨miRNA-215、miRNA-199对心房Cx40重构的调控机制及其在房颤发生中的作用，为房颤干预提供新靶点。

Some evidences have indicated that upregulation of miRNA-215 and miRNA-199 contributes to atrial fibrillation (AF). However, the mechanism of miRNA-215 and miRNA-199 involving in the pathogenesis of AF is unknown. Our previous studies show that Cx40 remolding plays an important role in AF. Nkx2.5 encoded by NKX2-5, a transcription factor, activates the transcription of GJA5 by binding its promoter. Interestingly, the NKX-2-5 and GJA5 encoding Cx40 are potential target genes for miRNA-215 and miRNA-199, respectively. We propose the hypothesis that miRNA-215 and miRNA-199 may take part in the pathogenesis for AF by regulating Cx40 in transcriptional and posttranscriptional level, respectively. To testify this hypothesis, The expression of miRNA-215，miRNA-199, Nkx2.5 and Cx40 will be measured in the patients with AF and the rapid atrial pacing canine models by RT-qPCR, immunofluorescence and Western-blot. The human atrial myocyte and mouse models of miRNA-215/miRNA-199 overexpression or underexpression will be made by miRNA mimic/inhibitor transfection and lentiviral vector transfection, respectively. The effect of miRNA-215/miRNA-199 overexpression or underexpression on the Nkx 2.5, Cx40 and AF susceptibility will be observed. Therefore, the effect of miRNA-215 and miRNA-199 on atrial Cx40 remolding in atrial fibrillation will be investigated to reveal the pathogenesis of AF and provide new targets for the intervention of AF.