miR-320家族在主动脉夹层血管重构中的作用及机制研究

项目名称： miR-320家族在主动脉夹层血管重构中的作用及机制研究

项目编号： No.81470576

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 廖明芳

作者单位： 中国人民解放军第二军医大学

项目金额： 73万元

中文摘要： 主动脉夹层（AD）破裂死亡率极高，严重威胁患者生命。我们前两个课题通过蛋白质组学和miRNA芯片等发现AD患者胸主动脉中膜差异表达蛋白和miRNAs，它们在AD血管病理性重构中可能具有重要作用，其中miR-320家族在AD中表达较对照组明显降低，应用miR-320 sponge转基因小鼠诱导AD较野生型小鼠更易发生夹层。本项目拟延续前期研究，采用ITRAQ蛋白质组学、表达谱芯片、分子生物学及生物信息学等技术，筛选出与AD可能密切相关的miR-320家族的靶基因/蛋白，并在体内小鼠模型和体外细胞中探讨其作用机制；进而利用miRNA过表达/沉默及miRNA sponge等技术，探讨miR-320家族作为AD发病过程中的可能干预靶点的应用价值。本项目从上游基因调控到下游蛋白功能水平进行研究，为阐明AD的发病机理提供新思路，并为AD的早期防治、疾病转归和预后评估提供可能的新靶标。

中文关键词： 主动脉夹层；血管重构；微小RNA

英文摘要： Aortic dissection (AD) is a life-threatening disease with high mortality in both early phases and in the long term especially in thoracic aortic dissection. We reported differentially expressed proteins and differentially expressed microRNAs(miRNAs) profiles of the aorta between AD patients and normal controls in our previous studies, which provide important information for the vascular pathological remodeling of AD. Among the differentially expressed miRNAs, the expression of miR-320 family including miR-320a,320b,320c and 320d decreased significantly compared with the normal control. We construct the miR-320 sponge transgenic mice and induced aortic dissection by angiotensin Ⅱ infusion and high fat diet in the transgenic mice and wild type mice. We found that the morbidity of aortic dissection was higher in the miR-320 sponge trangenic mice than that in the wild type mice.The results suggested that miR-320 family may play important roles in the vascular pathologic remodeling of AD, which deserve further research. In this program, we plan to discover the possible target gene and proteins of miR-320 by using ITRAQ proteomics, gene expression array, molecular biology and bioinformatic technique and et al. Then we will investigate the molecular pathogenesis of miR-320 family in AD in vivo and in vitro. The value of miR-320 as the target of interfering the process of AD will also be evaluated by techniques of miRNA overepression or knockdown as well as miRNA sponge. The resluts of this program will help give further new insight into the pathogenesis of AD and provide new possible target moleculars for early diagnosis or prevention and treatment for AD.

英文关键词： aortic dissection;vacular remodeling;microRNA