miR-146a和miR-181b在矽肺发生和纤维化中的调节作用研究

项目名称： miR-146a和miR-181b在矽肺发生和纤维化中的调节作用研究

项目编号： No.81202181

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 王发选

作者单位： 宁夏医科大学

项目金额： 23万元

中文摘要： 矽肺是严重危害劳动者职业健康的重要职业病，目前尚无有效治疗办法。矽肺发生的确切机制尚未阐明，多数认为与肺组织中细胞因子失衡有关。尤其是肿瘤坏死因子α（TNF-α），白介素1β（IL-1β）和转化生长因子β1(TGF-β1），三种细胞因子的动态变化影响着矽肺的发生和进展。MicroRNA能够调控转录和转录后翻译过程，是否参与矽肺发生发展过程有待研究。本课题前期研究发现矽肺组织和正常肺组织microRNA表达谱存在差异，借助生物信息软件预测可能作用于在矽肺发生发展中起关键作用的三种细胞因子的microRNA,结合芯片分析结果，选择miR-146a和miR-181b，利用分子生物学方法体外建立两种microRNA的过表达和抑制表达模型，分析miR-146a和miR-181b对三种细胞因子的影响。从新的视觉阐明miR-146a和miR-181b与矽肺发生和纤维化的关系，并为矽肺的防治提供新的思路。

中文关键词： 矽肺；纤维化；微小RNA；miR-146a；miR-181b

英文摘要： silicosis is a severe occupational disease that poses great threats to professional health with no effective cure.while the mechanism of its process has not been fully understood, many studies indicate its connection with cytokine disorder of lung tissue. the dynamic changes of TNF-α, IL-1β and TGF-β1 are found to be closely associated with the occurrence and progress of silicosis. microRNAs play an important role in both transcriptional and posttranscriptional regulation of genes.however, the knowledge of the role of miRNAs in silicosis is still limited. early research of this study showed differential expression profiles of miRNAs between silicosis and normal lung tissue. bioinformatics software was applied to predict microRNAs involed in the regulation of three cytokines above.taken differential expression profiles into consideration, miR-146a and miR-181b have finally been chosen as our target miRNAs. hypoexpression and hyperexpression models in vitro of two miRNAs will be established to analyse the relationship between target miRNAs and target cytokines, which could probably shed some light on the association of target miRNAs with silicosis and its therapy as well。

英文关键词： silicosis；fibrosis；microRNA；miR-146a；miR-181b