利用肾小球全基因组表达数据筛选治疗糖尿病肾病的药物  

Exploration of potential drugs for diabetic nephropathy with the genome-wide expression data

作　　者：史文潮 施劲松[1] 蒋松[1] 邱丹丹[1] 王晓[1] 刘志红[1] 

机构地区：[1]南京大学医学院附属金陵医院(南京军区总医院)肾脏科,国家肾脏病临床医学研究中心,全军肾脏病研究所,南京210016

出　　处：《肾脏病与透析肾移植杂志》2015年第3期249-254,共6页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：国家科技支撑计划项目课题(2013BAI09B04,2015BAI12B05);江苏省自然科学基金项目(BK2012054)

摘　　要：目的:利用2型糖尿病肾病(T2DN)患者微分离的肾小球全基因组表达数据,借助关联性图谱(CMAP)数据库和生物信息学方法,探寻具有T2DN治疗作用的潜在药物。方法:选取中国汉族T2DN患者23例和正常对照6例,微分离肾小球,利用Affymetrix U133 Plus 2.0全基因组表达谱芯片检测获得基因表达数据,获得T2DN患者不同分期之间的差异表达基因后,进一步通过2种不同的生物信息学方法寻找T2DN的潜在治疗药物,并阐明其可能的分子作用机制。结果:利用T2DN晚期和早期相比的差异表达基因和CMAP数据库,筛选出小白菊内酯(parthenolide)、荜茇酰胺(piperlongumine)、15-脱氧前列腺素J2(15d-PGJ2)和LY-294002(PI3K抑制剂)等候选药物。上述药物能够逆转T2DN患者在疾病进展过程中肾小球基因表达的变化,提示这些药物可能具有治疗T2DN的潜能。既往研究证实这些药物对T2DN有一定的治疗作用,验证了该药物筛选方法的可靠性。结论:利用T2DN患者肾小球全基因组表达谱和CMAP数据库能够快速筛选出具有T2DN治疗潜能的药物,候选药物可进行下一步的动物实验和临床试验以证实其治疗的安全性和有效性,应用前景广阔。Objective： To investigate potential drugs for diabetic nephropathy （DN） using whole-genome expression profile and the Connectivity Map （CMAP）. Methodology：Twenty three Chinese Han DN patients and six normal controls were included in this study. Whole-genome expression profiles of micro-dissected glomeruli were measured using the Mfymetrix human U133 plus 2. 0 chip. Differentially expressed genes （DEGs） between late stage and early stage DN samples and CMAP database were used to identify potential drugs for DN using bioinformaties methods. The molecular mechanisms of the potential drugs were also investigated. Results： Parthenolide, piperlongumine, 15d-PGJ2 and LY- 294002 were predicted to maximally reverse the disease-associated expression of genes in glomerular of DN patients. Additional literature analysis of published researches showed that these drugs had therapeutic potential for DN. Conclusion：Using whole genome expression profiles and the CMAP database, the potential drugs for DN were rapidly predicted, and therapeutic potential was confirmed by previously published studies. Animal experiments and clinical trials are needed to confirm both the safety and efficacy of these drugs in the treatment of DN.

关 键 词：糖尿病肾病 全基因组表达谱 关联性图谱 药物筛选 

分 类 号：R587.2[医药卫生—内分泌]