关键词:

阿维菌素, 疾病基因表达谱, 药物转录组, 高尿酸血症, 分子对接

Abstract:

Objective Drugs with anti⁃hyperuricemia were screened from old drugs by the strategy of new use of old drugs based on disease gene expression profile and drug transcriptome. Methods Hyperuricemia （HUA）transcriptome database was used to screen hyperuricemia differentially expressed genes，and the DAVID database and STRING platform were used to screen and analyze the differentially expressed genes. The predicted anti⁃HUA drugs were screened from the old drugs by the Connectivity Map database，the drugs with high enrich⁃ ment fractions were selected and differentially expressed core targets，and the SwissDock platform was used for molecular docking. The CCK⁃8 assay was used to detect the effect of candidate anti⁃HUA drugs on HK⁃2 cell viability， and to verify the effect of candidate drugs on xanthine oxidase activity and uric acid concentration in the HUA cell model. Results In the HUA transcriptome database，1 492 differential genes were obtained，including 810 down⁃ regulated genes and 682 up ⁃ regulated genes. The differential genes involved HDASC deacetylate histones，IL ⁃7， UB⁃specific processing proteases，and other pathways. The 15 drugs were predicted to have anti⁃HUA potential by the Connectivity Map database. Molecular docking showed that the binding energies of avermectin to the core targets IL⁃1β，TNF，CXCL2，and IL⁃6 were -7.68，-7.97，-6.25，and -6.73 kcal/mol，respectively. The results of cell experiments showed that avermectin had good cell safety，inhibited xanthine oxidase activity，and reduced uric acid in the concentration range of 12.5~100 μg/mL. Conclusions This present study found that the old drug abamectin has anti⁃hyperuric acid potential through a combination of disease gene expression profile and drug tran⁃ scriptome data.

Key words:

avermectin, disease gene expression profile, drug transcriptome, hyperuricemia, mo? lecular docking