中文摘要：

目的筛选、分析与非瓣膜性心房颤动（房颤）相关的微RNA（miRNA）。方法选择2009年1月至2010年12月北京安贞医院心外科的非瓣膜性房颤患者33例，应用低密度芯片技术，检测非瓣膜性房颤患者和健康人左心耳组织中miRNA表达谱的差异，用生物信息学方法筛选与房颤相关的miRNA及其靶基因，进一步通过定量反转录（RT）-PCR，Western印迹法和体外构建报告载体实验，验证miRNA和其靶基因之间的关系。结果与健康人比较，房颤患者左心耳组织中发现10个差异表达的miRNA：miR-155、miR-142-3p、miR-19b、miR-223、miR·146b-5p、miR-486—5p、miR-301b、miR-193b和miR-519b表达高，miR-193a-5p表达低（均P〈0．05）；其中miR-155表达差异最大（9．42±4．74比1．63±0．65），为健康人组织的5．78倍。miR．155的高表达导致了预测的靶基因CACNA1C和相应Cavl-2蛋白的低表达，体外构建报告载体实验发现miR-155可以结合到CACNA1C的3＇．UTR区。结论非瓣膜性房颤患者左心耳组织中存在与其发病相关的miRNA，其中miR-155有可能通过调控Cavl-2的表达，参与了房颤的电重构。

英文摘要：

Objective To detect the differential expressions of miRNAs in left atrial appendage （LAA） in patients with atrial fibrillation （AF）. Methods Left atrial samples were collected from nonvalvular AF patients and healthy controls. The miRNA transeriptome was analyzed by microarray and verified by real-time reverse transcription-polymerase chain reaction. Computational prediction identified the AF-related miRNAs and its target gene. In the meantime, construction of reporter plasmids and reporter assays were performed to test whether miRNA could represses the Luciferase activity of 3＇ untranslated regions of its target gene. Results MiR-155, miR-142-3p, miR-19b, miR-223, miR-146b-5p, miR486- 5p, miR-301b, miR-193b, miR-5t9b were found to be up-regulated by 〉 2 folds whereas miR-193a-Sp was down-regulated. In particular, the level of miR-155 increased by 5.78 folds in AF patients versus healthy controls （9. 42 ± 4.74 vs 1.63 ± 0. 65 ）. Furthermore, computational prediction identified CACNA1C encoding Cavl. 2 as a direct target of miR-155. In the meantime, the construction of reporter plasmids and reporter assays showed that miR-155 repressed the Luciferase activity of 3＇ untranslated regions of CACNA1C. Conclusion In LAA sample of nonvalvular AF, there is an expression of AF-related miRNAs including miR-155. And it reveals a potential link between the regulation of Cavl. 2 and miR-155 in electric remodeling of AF.