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| Prediction of therapeutic drugs for diabetic nephropathy based on disease gene expression profiling |
| SHI Xiaoxian1 LI Gaowen2 |
1.Department of Pharmacy, Li Huili Hospital, Ningbo Medical Center, Zhejiang Province, Ningbo 315040, China;
2.Ningbo College of Health Sciences, Zhejiang Province, Ningbo 315000, China |
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Abstract Objective To explore the application effects of gene expression profiling in screening the effective therapeutic drugs for diabetic nephropathy. Methods The gene chips related to diabetic nephropathy in GEO databases were searched and the differential gene expression was analyzed by d-chip software. Enrichment analysis of the relevant signaling pathways was carried out by GSEA, Cmap was then used for the screening of candidate drugs of diabetic nephropathy and pharmacodynamic validation was evaluated in animal experiments. Results Through the analysis of differential genes in qualified samples from the GSE31022 chip, a total of 540 genes were obtained, of which, 150 genes were up-regulated and 390 genes were down-regulated. The main enrichment to NF-κB signaling pathway by GSEA was most closely related to diabetic nephropathy (P ＜ 0.05), and screening for Thiamphenicol may have a therapeutic effect on diabetic nephropathy (score=1). The results of animal experiments showed that compared with model group, the mesangial expansion of the diabetic nephropathy mice treated by Thiamphenicol was significantly improved and almost reached the normal level (P ＜ 0.05). In addition, the levels of urine protein and the mRNA levels of CD68, transforming growth factor β, plasminogen activator inhibitor 1 and interleukin 6 in the Thiamphenicol group were significantly lower than those in model group (P ＜ 0.05). Conclusion As an effective means of predicting effective therapeutic drugs for diabetic nephropathy, the gene expression profiling based on diabetic nephropathy provides a new idea for the discovery of therapeutic drugs for the disease.
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