中性粒细胞型哮喘差异表达基因的生物信息学分析及其潜在治疗药物筛选

Bioinformatics analysis on differential expression genes of neutrophilic asthma and drug screening

目的运用生物信息学方法与分子对接技术筛选中性粒细胞型哮喘(neutrophilic asthma,NA)的差异表达基因(DEGs)及其潜在治疗药物,为其治疗提供新的靶点和药物。方法从GEO数据库筛选NA与健康人群的DEGs,通过STRING数据库构建DEGs的蛋白互作(PPI)网络筛选关键基因,并对DEGs进行GO功能注释与KEGG通路富集分析,采用分子对接技术筛选潜在的先导化合物。结果共筛选出147个DEGs;PPI网络分析筛选出CXCL8、FPR2、CXCL1、TNFRSF1B、CXCR1等10个关键基因;GO分析表明DEGs参与炎症与免疫反应、趋化作用等生物过程;KEGG通路分析显示DEGs主要富集于细胞因子-细胞因子受体相互作用、补体与凝血等信号通路;分子对接显示芍药苷元酮与雷公藤甲素与补体与凝血通路中C8B、PLAU等基因蛋白具有很好的结合活性。结论本研究发现补体与凝血信号通路或许可以成为NA新的治疗靶点,芍药苷元酮与雷公藤甲素是潜在的治疗药物。

Aim To explore the differential expression genes(DEGs)and potential therapeutic drugs of neutrophilic asthma(NA)based on bioinformatics analysis and molecular docking.Methods The gene expression profiles of NA were obtained from GEO database,and the differential expression genes were screened.The protein-protein interactions(PPI)of DEGs were obtained from STRING database,and the hub genes were screened by Cytoscape according to the degree of DEGs.The GO and KEGG pathway analysis were performed by DAVID database.Finally,molecular docking technology was used to screen the potential therapeutic drugs for the treatment of NA.Results A total of 147 DEGs were obtained from NA patients compared with healthy people in GEO database.Ten hub genes were screened from PPI network,including CXCL8,FPR2,CXCL1,TNFRSF1B,CXCR1,etc.Go enrichment analysis showed that DEGs were mostly associated with inflammation,immune response and chemotaxis,etc.KEGG pathway analysis indicated that the DEGs were mainly involved in cytokine-cytokine receptor interaction and complement and coagulation signaling pathways.Molecular docking showed that paeoniflorigenone and triptolide had good binding activity with C8B and PLAU.Conclusion Complement and coagulation cascades may become a new therapeutic target of NA.The two screened compounds paeoniflorigenone and triptolide may be potential therapeutic drugs for the treatment of NA.