miRNA-223抑制Pknox1基因调控糖尿病脂质代谢的分子机制研究

项目名称： miRNA-223抑制Pknox1基因调控糖尿病脂质代谢的分子机制研究

项目编号： No.81500616

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 叶丹

作者单位： 浙江大学

项目金额： 18万元

中文摘要： 我们前期发现， miR-223的表达在2型糖尿病伴非酒精性脂肪肝的患者中较单纯糖尿病患者血浆中明显下调，表达改变更先于肉眼可见的组织病理学变化及外周血清学指标，而且通过miRNAS微阵列分析亦发现糖尿病伴非酒精性脂肪肝的大鼠较单纯糖尿病大鼠中血浆和肝脏组织中miR-223的表达明显下降。本项目拟更深一步研究miR-223作为功能性的调节因子在糖尿病和高脂状态的病理生理中的作用机制，研究miR-223在人体内和动物模型中对糖尿病血糖水平和脂质代谢、胰岛素抵抗的调控作用，并在细胞和分子水平揭示其调控血糖和胰岛素抵抗的蛋白靶点，联合miRNA靶基因的预测分析，明确miR-223是否通过调控Pknox1靶基因编码的PREP1蛋白水平，影响脂质合成和分解的关键酶（SREBP1、FAS、ACC1、HMGR）调节脂质代谢，参与到2型糖尿病脂肪肝的发生发展，并探讨作为外周血可能的miRNA标记及预警新指标

中文关键词： 糖尿病；小RNA；胰岛素抵抗；脂代谢；脂肪肝

英文摘要： We found in earlier study, a significant down-regulation of miR-223 expression in non alcoholic fatty liver disease with type 2 diabetes mellitus compared with type 2 diabetes mellitus, and this change precede the visible histological changes and peripheral serum index. By miRNAs microarray analysis , we also found that in diabetic mellitus with non alcoholic fatty liver diease rats compared pure type 2 diabetes rats, miR-223 in plasma and liver tissue significantly decreased. This project aims to further study the regulation of miR-223 in blood glucose and insulin resistance as a functional mechanism in diabetes and non alcoholic fatty liver disease through animal models and in cell and molecular level , and predictive analysis combined with target genes of miRNA,we want to verify whether miR-223 through Pknox1 target genes regulating lipid metabolism which involving in the occurrence and development of non alcoholic fatty liver disease with type 2 diabetes mellitus, and expected the possibility of miR-223 as peripheral blood miRNA markers and early warning index.

英文关键词： Diabtes;miRNA;insulin resistance;adipose metabolism;fatty liver