糖基化终末产物对tTG的影响及其在糖尿病肾病发病中的作用

项目名称： 糖基化终末产物对tTG的影响及其在糖尿病肾病发病中的作用

项目编号： No.30800423

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 于晓艳

作者单位： 吉林大学

项目金额： 20万元

中文摘要： 在糖尿病持续高血糖状态下，糖基化终末产物（AGEs）形成明显增加， 即使血糖恢复正常，AGEs也持续存在并对机体产生危害。动物和人类糖尿病肾脏的AGEs含量明显升高，可从促进合成和减少降解两方面引起细胞外基质（ECM）积聚，在糖尿病肾病的发病机制中起重要作用。组织型转谷氨酰胺酶( tTG )可使ECM蛋白被修饰而抵抗蛋白酶的降解。糖尿病状态下，肾脏tTG表达和活性增加并且与增加的ECM呈正相关，但至于tTG的改变是否与AGEs有关，如果有关，其在糖尿病肾病发生中的作用，是本项目的研究主要研究目标。在本项目中我们利用整体动物研究分析糖尿病及非糖尿病状态下tTG与AGEs的关系，利用体外对肾小球系膜细胞和肾小管上皮细胞的研究探讨tTG与AGEs二者之间的可能分子机制。为糖尿病肾病的发病机制提供理论基础。

中文关键词： 糖基化终末产物；糖尿病肾病；组织型转谷氨酰胺酶；细胞外基质

英文摘要： In prolonged hyperglycemia state, formation of Advanced glycation end products（AGEs）increas.Excessive formation of AGEs brings hazardous effects to organism even though blood glucose put back. In kidney of diabetic human or animal, AGEs content rise obviously. Excessive formation of these proteins induces extracellular matrix accumulation through promoting synthesis and decreasing degradation, which play a important role in the pathogenesis of diabetic nephropathy. Tissue-transglutaminases(tTG) can make ECM protein resist proteinase. Under diabetic condition, expression and activity of tTG increase, further more, excessive tTG has a positive correlation with ECM accumulation. However,whether does it exsist a association between tTG and AGEs;if the association exsist,its role in the pathogenesis of diabetic nephropathy. In this study, these are our objective. In vivo, we investigate the association between tTG and AGEs under diabetic status as well as non-diabetic status (animals were given AGEs). In vitro, we investigate the probable molecule mechanism using Mesangial cell and renal tubular epithelial cell. We hope these results will be helpful to interpret the pathogenesis of diabetic nephropathy.

英文关键词： Advanced glycation end products;diabetic nephropathy;Tissue-transglutaminases;extracellular matrix