预测miRNA在原发性高血压合并2型糖尿病的治疗靶点研究

项目名称： 预测miRNA在原发性高血压合并2型糖尿病的治疗靶点研究

项目编号： No.81460076

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： 杨红菊

作者单位： 昆明医科大学

项目金额： 50万元

中文摘要： 原发性高血压（EH）合并2型糖尿病（T2DM）是并发心脑血管病多、治疗难度大的常见多基因遗传疾病，开展与EH合并T2DM发病密切相关的胰岛素抵抗调控基因研究，对阐明其遗传发病机制、风险评估、愈后判断、预防及基因治疗靶点筛选均具有重要意义。我们近年在对AGTR1、CMA1等基因多态与云南人群EH发病相关的研究基础上，提出miRNA参与EH合并T2DM及并发症发生靶基因表达调控的假说。通过研究miRNA调控靶基因的表达来验证假说，探索与胰岛素抵抗作用相关miRNA信号通路，揭示云南汉族EH合并T2DM发病的分子机制，预测miRNA治疗该疾病的作用靶点； miRNA差异表达可能作为EH合并T2DM及并发症发生判定参考指标之一，此法目前国内外文献未见报道，本研究首次揭示miRNA调控靶基因表达可能是EH合并T2DM及并发症发生的分子机制，为其防治提供理论依据，并为应用于临床治疗提供新的思路。

中文关键词： 微小RNA；原发性高血压合并2型糖尿病；分子机制；治疗靶点

英文摘要： 。Essential hypertension(EH) complicated with type 2 diabetes mellitus（T2DM） is a kind of common polygenic inherited disease, which may induce cardio-cerebrovascular disease.Carrying out the research on the gene regulatory mechanism of the insulin resistance significantly associated with EH complicated with T2DM is important to clarify the genetic pathogenesis of the disease, the risk assessment, the evaluation of the prognosis, the prevention of the disease and screen the therapeutic target of genes. Based on the research of the association of AGTR1,CMA1 gene polymorphisms with essential hypertension in populations of Yunnan province, we hypothesis that microRNAs are involved in the regulation of target gene expression related to the occurrence of the EH Complicated with T2DM. Finally, we could verify the hypothesis we proposed before, explore the signal pathway of microRNA regulatory mechanism of the insulin resistance, reveal the molecular mechanism of the occurrence of the EH complicated with T2DM in populations of Yunnan province, and predict the therapeutic target of microRNA by researching on target gene expression regulated by microRNA. The differential expression of microRNA can be used as one of the diagnostic criteria of EH complicated with T2DM. At present, we have not seen the relevant report at home and abroad. This study for the first time reveals that microRNA regulatory mechanism of target gene expression is likely to be the molecular mechanism of the occurrence of the EH complicated with T2DM. It can provide theoretical basis for the prevention and treatment of EH complicated with T2DM, and put forward new ideas for the application in clinical treatment.

英文关键词： miRNA;essential hypertension with type 2 diabetes mellitus;molecular mechanisms;therapeutic targets