miR-98及调节相关因子在Ⅱ型糖尿病大动脉早期病变中的作用

项目名称： miR-98及调节相关因子在Ⅱ型糖尿病大动脉早期病变中的作用

项目编号： No.81200601

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 王萍玉

作者单位： 滨州医学院

项目金额： 23万元

中文摘要： 大血管病变是糖尿病个体致死、致残的主要原因之一，具体的病变机制尚不清楚。研究表明miRNA在糖尿病中起重要作用。 前期研究，我们发现与对照组相比，miR-98在糖尿病GK大鼠大动脉内膜、外膜表达都明显降低。通过microRNA软件分析发现，miR-98调节的因子可能有Cyclin D2、TRB2等。进而构建了pcDNA-GFP-UTR载体，与miR-98共转染大鼠内皮细胞株，结果表明miR-98对TRB2-3'-UTR起调控作用，而TRB2在Ⅱ型糖尿病大鼠模型大血管内膜和外膜表达量都明显增高，说明二者参与了糖尿病大血管病变过程。在上述基础上，本课题将利用分子生物学、免疫学等技术，从细胞和个体水平，深入研究miR-98对TRB2、Cyclin D2及相关因子的调节作用，进而分析miR-98及相关因子在Ⅱ型糖尿病大动脉早期病变中的作用，为Ⅱ型糖尿病血管病变的预防和治疗提供新的靶点和科学资料。

中文关键词： 2型糖尿病；微RNA；大血管病变；基因表达；

英文摘要： The large artery complication could cause the main death and disable to diabetic individual. However, the mechanisms involved in the pathogenesis of vascular complications in Non-insulin-dependent diabetes mellitus (NIDDM, type-2 diabetes).NIDDM are poorly understood. Many studies showed that the important roles of miRNA in pathogenesis of diabetes. In precious study, we found that the expression of miR-98 was decreased obviously in the adventitia and the endomembrane in the diabetic GK rats compared with control groups. The regulating factors of miR-98 may be TRB2 and CyclinD2 by using microRNA TargetScan software analysis. After the reporter plasmid (pcDNA-GFP-UTR vector) was constructed, miR-98 was co-transfected with the reporter plasmid into rat RAOEC cells. The intensities of ?uorescence from the miR-98 groups were all decreased in comparison to the control group, which indicated that miR-98 could regulate TRB2-3'-UTR expression. TRB2 expression was found to be highly upregulated in the aorta wall of GK rat compared with the Wistar rat, which support that miR-98 and TRB2 attend the artery pathogenesis of diabetes. Based on precious study，we futher explore the roles of miR-98 in regulating the TRB2/Cyclin D2 by molecular biology or immune methods, and analyze roles of miR-98 and its relative factors in the

英文关键词： Type-2 diabetes；miRNA；large artery complication；Gene expression？；