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 explore the genome-wide glomerulus differential expression profiles in patients with type 2 diabetic nephropathy (T2DN) and to explore potential therapeutic agents for T2DN therapy with the help of the Association Map (CMAP) database and bioinformatics methods. Methods: Twenty-three T2DM patients in Han nationality and 6 normal controls were selected and differentiated into glomerulus. Affymetrix U133 Plus 2.0 genome-wide expression microarray was used to detect gene expression data. After differentially expressed genes in T2DM patients were obtained, Further search for potential therapies for T2DN by two different bioinformatics methods and elucidate the possible molecular mechanisms of action. Results: Parthenolide, piperlongumine, 15-deoxy-prostaglandin J2 (15d-PGJ2) and LY-294002 were screened by using differentially expressed genes in T2RD late and early stages and CMAP database PI3K inhibitor) waiting for drug selection. The above drugs can reverse the changes of glomerular gene expression in patients with T2DN during the progression of the disease, suggesting that these drugs may have potential for the treatment of T2DN. Previous studies confirmed that these drugs have a certain therapeutic effect on T2DN, which verifies the reliability of the drug screening method. Conclusion: The glomerulus genome-wide expression profile and CMAP database of patients with T2DM can be used to rapidly screen out the potential therapeutic drugs for T2DN. The candidate drugs can be used for further animal experiments and clinical trials to confirm the safety and efficacy of the treatment. Broad prospects.