miRNA-590-3p调控的PDGF-BB信号通路在心房重构致心房颤动中的作用研究

项目名称： miRNA-590-3p调控的PDGF-BB信号通路在心房重构致心房颤动中的作用研究

项目编号： No.81460057

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 钟国强

作者单位： 广西医科大学

项目金额： 47万元

中文摘要： Cx43重构及心房纤维化引起的心房电重构及结构重构是房颤发生的重要机制。我们前期的研究工作发现血小板衍生生长因子（PDGF）参与Cx43重构及心房纤维化，微小RNA-590-3p(miR-590-3p)是重要的抗纤维化因子，PDGF-B是miR-590-3p的潜在靶基因。因此，假设由于不同原因下调的miR-590-3p参与了PDGF-BB信号通路的调控，导致Cx43重构及心房纤维化而致房颤，相关的研究尚未见文献报道。我们将采用RT-qPCR、Western-blot检测房颤患者、快速心房起搏房颤犬心房miR-590-3P、PDGF-BB、Cx43、I型胶原，双荧光素酶报告基因系统验证PDGF-B是miR-590-3p调控靶基因，慢病毒转染构建miR-590-3p过表达及抑制表达小鼠模型，探讨miR-590-3p调控的PDGF-BB信号通路在心房重构中的作用机制，为房颤的防治提供新的思路。

中文关键词： 心房颤动；心房重构；微小RNA；血小板衍生生长因子

英文摘要： Atrial structural and electrical remodeling caused by Cx43 remodeling and atrial fibrosis play a part in the atrial fibrillation. Our previous research showed that the Platelet derived growth factor (PDGF) mediated the Cx43 remodeling and atrial fibrosis. MicroRNA-590-3p(miR-590-3p) is an important anti-fibrotic factor, PDGF-B as a target gene of miR-590-3p. Therefore we hypothesize that down-regulation of miR-590-3p can lead to the atrial fibrillation via Cx43 remodeling and atrial fibrosis by activating thePDGF-BB signaling pathway.There is none of the report for the related research in the literature.The miR-590-3p，PDGF-BB，Cx43，CollagenⅠwill be measured for the patients with atrial fibrillation and rapid atrial pacing canine models by RT-qPCR、Western-blot; Dual luciferase reporter gene assay kit will verify PDGF-B as a target gene of miR-590-3p; miR-590-3p overexpression or underexpression mouse models will be made by lentiviral vector transfection. This study is to lay the foundation for revealing the pathogenesis of atrial fibrillation and provide new strategies for the prevention and treatment of atrial fibrillation.

英文关键词： Atrial fibrillation;atrial remolding;microRNA;Platelet derived growth factor(PDGF)