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目的研究与糖尿病肾病(DN)进展相关的肾小球基因表达谱及其可能的致病机制。方法将DN患者根据蛋白尿、肾小球组织病理学改变和Scr水平分为不同的临床表型组。5例正常对照来自供肾。留取少许肾活检组织,显微镜下分离肾小球,RNA体外线性扩增。采用Affymetrix基因芯片建立DN患者肾小球基因表达谱,以生物信息学方法分析。用实时PCR技术验证基因芯片结果。结果不同临床表型的DN患者表现出不同的肾小球基因表达谱。整合3组不同临床表型基因表达谱中共有的变化规律,筛选出与DN疾病进展相关的139个基因。其中表达改变涉及最多的是与糖、脂质代谢相关的基因,其表达水平呈现一致性的下调;表达改变最为显著的是与炎症相关的分子。结论大量蛋白尿、肾小球节段硬化和Scr升高等与DN疾病进展相关的临床表型伴有肾小球基因表达谱的改变。在DN进展中,糖代谢和脂质代谢同时发生紊乱,相关基因表达水平一致下调。细胞能量代谢紊乱及继发的局部炎症反应也发挥了重要作用。
Objective To investigate the gene expression profiles of glomeruli associated with the progression of diabetic nephropathy (DN) and its possible pathogenesis. Methods DN patients were divided into different clinical phenotype groups according to proteinuria, glomerular histopathological changes and Scr levels. Five normal controls came from the kidneys. A small amount of renal biopsy was taken and glomerulus was separated under microscope. RNA was amplified linearly in vitro. Gene expression profiles of glomeruli in patients with DN were established using Affymetrix GeneChip and analyzed by bioinformatics methods. Real-time PCR technology to verify gene chip results. Results DN patients with different clinical phenotypes showed different glomerular gene expression profiles. The changes of common clinical phenotypes in three groups were integrated and 139 genes related to the progression of DN were screened out. Among them, the genes involved in glucose metabolism and lipid metabolism are most involved in the expression changes, and their expression levels are consistently down-regulated. The most significant changes are the inflammation-related molecules. Conclusions A large number of proteinuria, glomerular segmental sclerosis and Scr elevated clinical phenotypes associated with the progression of DN were associated with altered glomerular gene expression profiles. In the progress of DN, glucose metabolism and lipid metabolism disorder at the same time, the related gene expression level down. Disorders of cellular energy metabolism and subsequent local inflammatory responses also play an important role.