摘要
目的 :研究糖尿病肾病 (diabeticnephropathy ,DN)患者肾小球基因表达谱与正常人之间的差异 ,及其在DN病程进展中的变化。 方法 :选择分别处于微量白蛋白尿期 ,临床蛋白尿期及伴有肾功能损害期的 3例DN患者 ,并以性别、年龄与患者匹配的 2例正常供肾组织作为对照。首次应用显微微分离法获取肾活检标本中的肾小球 ,进行肾小球细胞数目扩增 ,利用AffymetrixU133A基因芯片技术检测其基因表达谱的变化 ,以生物信息学工具作聚类分析。 结果 :与正常对照组相比 ,DN患者肾小球内表达水平显著上升或下降的基因共有 182条(P <0 0 1)。聚类分析将显著差异表达基因群分为表达水平显著升高、表达水平下降和持续性显著下降三个特殊亚群。功能分析发现 ,DN患者肾小球基因表达谱的变化突出表现在某些与细胞内异常糖和脂质代谢、细胞增殖、细胞外基质合成和细胞因子相关基因上 ,特别是脂质代谢相关基因。部分基因的表达变化与DN病情进展有一定相关性 ,存在随病情进展表达水平逐渐增加、在DN病程早期应答和随病情进展表达水平逐渐下降的三组基因。未发现转化生长因子 β1在DN患者肾小球细胞内mRNA表达水平呈现显著变化。 结论 :与正常人相比 。
Objective:To compare the differences of glomerular gene expression profiles between patients with diabetic nephropathy (DN) and normal controls, and to investigate its changes in the progression of DN. Methodology:Three DN patients presented respectively with microalbuminuria, overt proteinuria or renal function damage were selected in order to clarify the relationship between the gene expression profiles and the clinical course. Normal donor kidneys were used as controls and were sex and age matched with the patients. Total RNA was isolated from glomeruli and applied for gene expression profiling by Affymetrix U133A arrays. Results:A total of 182 genes varied significantly in glomeruli derived from DN patients, comparing with the normal controls (P<0.01). There were 3 distinct patterns within the 182 genes appeared as up-regulated pattern, down-regulated pattern and one special pattern including genes with extremely lower expression in DN patients. The 182 genes were involved primarily in cellular glucose metabolism, lipid metabolism, extra-cellular matrix modulation, cell proliferation and some cytokines, especially in lipid metabolism. Some genes varied in parallel with the severity of clinical manifestations in the patients. Interestingly, the mRNA level of TGF-β1 did not change obviously in the glomeruli taken from DN patients. Conclusion:We first reported the gene expression profiles of glomeruli obtained from patients with DN. It was highlighted point that the genes related to glucose metabolism, lipid metabolism, extracellular matrix modulation, cell proliferation and some cytokines were changed in the gene expression profile of DN glomeruli. The fluctuation of some DN-related gene levels has relationship with the clinical course of DN.
出处
《肾脏病与透析肾移植杂志》
CAS
CSCD
2004年第6期503-511,共9页
Chinese Journal of Nephrology,Dialysis & Transplantation
基金
军队"十五"重点课题资助项目 (0 1Z0 13 )
