miR-34a/myc/E2F1信号轴调控树突状细胞成熟和迁移的机制及黄芪多糖的干预研究

项目名称： miR-34a/myc/E2F1信号轴调控树突状细胞成熟和迁移的机制及黄芪多糖的干预研究

项目编号： No.81202951

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 靳文

作者单位： 南方医科大学

项目金额： 22万元

中文摘要： 动脉粥样硬化（atherosclerosis，AS）是冠心病的病理基础，树突状细胞成熟并迁移至AS病变处是促进AS进展的关键环节。但是，在AS条件下，树突状细胞获得成熟和迁移机制尚未阐明。本课题组研究发现黄芪多糖可抑制冠心病患者外周血单核细胞源性树突状细胞的成熟和迁移。本项目基于前期研究和E2F1抑制树突状细胞成熟和迁移的可能机制提出"在AS条件下黄芪多糖通过作用于miR-34a/myc/E2F1信号轴抑制树突状细胞成熟和迁移假说"。为验证上述假说，本项目拟采用RNA干扰、Western-blot、定量PCR等技术从体内和体外两方面对miR-34a/myc/E2F1信号轴在树突状细胞成熟和迁移中的作用及黄芪多糖的干预机制进行研究。本项目对进一步发掘AS的发病机理、治疗靶点及有效药物，丰富黄芪多糖抗AS的疗效机理，为AS的防治探索一条新的思路与途径。

中文关键词： 动脉粥样硬化；黄芪多糖；miR-34a；E2F1；树突状细胞

英文摘要： Atherosclerosis (AS) is the basic pathology of coronary heart disease. The maturation and migration into atherosclerotic lesions of dendritic cells (DCs) is the key step in promoting the progression of AS. However, little information is known about the mechanism of DCs acquiring maturation and migration under conditions of AS. Our previous studies showed that Astragalus Polysaccharides could suppress the maturation and migration of DCs derived from peripheral blood mononuclear cells in patients with coronary artery disease. Based on our previous studies and the underlying mechanisms of E2F1 suppressing the maturation and migration of DCs, we make a hypothesis that Astragalus Polysaccharides suppresses the maturation and migration of DCs by inhibiting miR-34a/myc/E2F1 signaling axis under conditions of AS. To verify this hypothesis, experimental techniques such as RNA interference, Western-Blot, quantitative PCR and so on, are taken to investigate the roles of miR-34a/myc/E2F1 signaling axis in the maturation and migration of DCs and the mechanisms of Astragalus Polysaccharides suppressing the maturation and migration of DCs in vitro and in vivo. This research intend to further explore the pathogenesis, therapeutic target and effective drug of AS, enrich the anti-atherosclerotic mechanism of astragalus polysaccha

英文关键词： atherosclerosis；astragalus polysaccharide；miR-34a；E2F1；dendritic cell