尿胞外体在糖尿病肾小管损害早期诊断中的作用研究

项目名称： 尿胞外体在糖尿病肾小管损害早期诊断中的作用研究

项目编号： No.81500554

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： 孙爱丽

作者单位： 山东大学

项目金额： 18万元

中文摘要： 中文摘要：糖尿病肾病往往首先引起肾小管细胞的损伤或者是在引起肾小球病变的同时也引起肾小管细胞的损伤。现已证实胞外体中包含大量与疾病相关的蛋白质。研究亦证实近曲肾小管上皮细胞分泌大量胞外体。因此本研究期望能发现反映糖尿病肾病早期损伤的标志物。体外研究：主要人近曲肾小管上皮原代培养细胞为模型，在体外分别应用高糖、缺氧、药物等因素干预，利用独有的胞外体抗体对不同时间点各组上清液中的胞外体进行蛋白质组学分析，并从中筛选肾小管细胞损伤特异性生物学标志物，进一步分析胞外体在各种病理因素下的变化及作用，用ELISA法在胞外体上检测尿调蛋白、E-钙粘蛋白、单核细胞趋化蛋白-1及其它炎症因子等的含量。临床研究：收集正常人、糖尿病肾病各期临床病例共240例，观察尿胞外体结合及游离尿调蛋白、E-钙粘蛋白、单核细胞趋化蛋白-1、白介素1B等，并分析之间的相关性及与肾病各期的相关性。

中文关键词： 尿胞外体；糖尿病；肾小管损害；早期诊断

英文摘要： Diabetic kidney disease is the leading cause of end-stage renal disease .Its central pathological feature is renal tubular cell injury or following with glomerular lesions.Immune dysfunction exists in the kidney tissues. Exosomes are spherical structures composed with a lipid bilayer carrying a cargo of proteins and nucleic acids,released by cells into extracellular space. In the study, we aim to clarify the expression of the quantity and location of exosomes in the renal tissues of normal and diabetic kidney disease,in the meanwhile, conduct the detection of urinary uromodulin ， E-cadherin，Monocyte Chemo-attractant Protein-1，et al by the techniques of ELISA. We will determine the relationship between the development of diabetic kidney disease and urinary exosomes through clinical study.240 cases including normal people,people with diabetes without nephropathy and people with different stages of diabetic kidney disease will be obtained to observe the levels of exosome-binding and free uromodulin, E-cadherin，Monocyte Chemo-attractant Protein-1, transforming growth factorβ1, etc.We will analyze the correlation among all the indicators and the relationship between the indicators and the development of diabetic kidney disease.

英文关键词： Urinary exosome;Diabetes mellitus;Renal tubular injury; early diagnosis