摘要
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 get more insight into progression of diabetic nephropathy （DN） and select individual genes associated with the progression of the disease. Methods Ten patients diagnosed as type 2 DN were included in the study. They were divided based on their clinical phenotype. Five donor kidneys served as normal controls. Glomeruli were dissected out from each individual patient abundant residual biopsy sample under microscope. Total RNA was extracted and biotin-labeled cRNA was hybridized to each GeneChip Human Genome U133 Plus 2.0 （Affyraetrix, Santa Clara, CA, USA）. Statistical analysis was performed with the GeneSpring 7.2 software （Silicon Genetics, Redwood City, CA, USA） and the further bioinformatic analysis was carried out. The alteration of candidate genes was further confirmed using real-time PCR. Results The glomerular gene profiling of DN was markedly distinct from the normal controls. Different genotypes were given based on the different clinical phenotypos. Combined analyzing the changed gene expression in the development of proteinuria, histology lesions and serum creatinine level, the gene profiling linked to the progression of DN was found, in which there were a lot of genes related to the metabolism. And some molecules related to inflammation response were also included. Conclusions Phenotypo-based analysis of glomerular gene profiling using biopsy tissues displayed the gene profiling of patients with progressive DN. Disordered metabolism and the following triggered inflammation response may play an important role in progression of DN.
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
2006年第9期528-534,共7页
Chinese Journal of Nephrology
基金
江苏省六大人才高峰项目[苏卫科教(2005)6号]
关键词
糖尿病肾病
基因芯片
表型
肾活检
代谢紊乱
炎症
Diabetic nephropathy
DNA microarray
Phenotype
Renal biopsy
Metabolism dysfunction
Inflammation response
