永久性心房颤动患者左心房差异基因表达谱的建立与分析

发布时间：2018-07-15 20:51

【摘要】：目的:探讨与永久性心房颤动(p AF)发生、发展相关的基因和信号通路,为研究p AF发生的分子机制提供基础。方法:用Agilent 4x44K基因芯片分析p AF患者(n=7例)与窦性心律健康者(n=4例)的左心房组织m RNA,寻找差异表达的基因。以Gene Ontology(GO)和KEGG、Biocarta数据库为基础,分析差异表达基因参与的功能和信号通路。选取差异显著的部分基因应用实时定量-聚合酶链式反应(q RT-PCR)在5例p AF患者与5例窦性心律健康者标本进行验证。结果:表达谱结果显示,共有987个差异表达基因,其中567个基因表达下调,420个基因表达上调。选取9个差异显著的基因在新一组的病例标本上应用q RT-PCR验证,结果显示均有统计学差异,且改变与芯片结果一致。这些基因通过参与左心房组织纤维化、电重构、炎症、细胞应激、代谢调节、转录调节等与p AF的发生密切相关。GO和Pathway分析表明下调的基因主要参与调节代谢,表达上调的基因影响细胞应激反应、免疫应答、血小板活化等过程。结论:通过基因芯片技术发现与p AF发生相关的重要基因,通过影响细胞代谢、炎症、免疫应答、血栓形成等参与左心房的结构、功能重构。
[Abstract]:Aim: to explore the gene and signal pathways related to the occurrence and development of permanent atrial fibrillation (PAF), and to provide a basis for studying the molecular mechanism of PAF. Methods: Agilent 4x44K gene microarray was used to analyze the mRNAs in left atrium of 7 patients with Agilent and 4 healthy subjects with sinus rhythm, and the differentially expressed genes were found. On the basis of Gene Ontology (go) and KEGGfBiocarta database, the function and signaling pathway of differentially expressed genes were analyzed. Some genes with significant difference were selected for real-time quantification-polymerase chain reaction (Q RT-PCR) to be tested in 5 patients with pAF and 5 healthy controls. Results: the expression profile showed that there were 987 differentially expressed genes, 567 of which were down-regulated and 420 were up-regulated. Nine genes with significant difference were selected to be confirmed by Q RT-PCR in a new group of patients. The results showed that there were statistical differences and the changes were consistent with the results of microarray. These genes involved in left atrial fibrosis, electrical remodeling, inflammation, cellular stress, metabolic regulation, transcriptional regulation and so on were closely related to the occurrence of pAF. Go and Pathway analysis showed that down-regulated genes were mainly involved in regulating metabolism. The up-regulated genes affect cell stress response, immune response, platelet activation and so on. Conclusion: the important genes associated with the development of pAF were found by gene chip technique, and involved in the structural and functional remodeling of left atrium by influencing cell metabolism, inflammation, immune response and thrombosis.
【作者单位】：首都医科大学附属北京朝阳医院心外科;
【基金】：北京市教委科技面上项目(SQKM201410025018)
【分类号】：R541.75

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