目的:探讨与永久性心房颤动(pAF)发生、发展相关的基因和信号通路,为研究pAF发生的分子机制提供基础.方法:用Agilent 4x44K基因芯片分析pAF患者(n=7例)与窦性心律健康者(n=4例)的左心房组织mRNA,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(qRT-PCR)在5例pAF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qRT-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pAF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pAF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.%Objective: To explore the relevant gene, signaling pathway for permanent atrial fibrillation (pAF) occurrence in order to provide the molecular basis of the pathogenesis of pAF. Methods: Our research included in 2 groups: pAF group, n=7 patients and Control group, n=4 healthy subjects with sinus rhythm. Agilent 4x44K microarray was used to analyze the mRNA in left atrium for differential gene expression profile. Based on Gene Ontology, KEGG and Biocarta databases, differentially expressed genes were studied for their relevant function and signaling pathway. Furthermore, the genes with significant differences were verified by quantitative real time PCR (qRT-PCR) in pathological specimen from 5 pAF patients and 5 normal heart donors. Results: The expression profile identified 987 abnormally expressed genes, 567 of them were down-regulated and 420 were up-regulated. 9 genes with significant differences were verified by qRT-PCR in pathological specimen and the changes were similar to microarray; those genes were closely related to pAF by involving left atrium fibrosis, electrical remodeling, inflammation, cellular stress response, metabolism and transcription regulation. GO and Pathway analysis indicated that down-regulated genes were mainly involved in metabolic processes; up-regulated genes had the effects on cellular stress response, immune response and platelet activation. Conclusion: Microarray technology identified some important genes related to pAF occurrence; such genes involved in left atrial structural and functional remodeling via affecting cellular metabolism, inflammation, immune response and thrombogenesis in relevant patients.
展开▼
