基于生物信息学探讨犀角地黄汤治疗银屑病的作用机制

Functional Mechanism of Xijiao Dihuang Decoction in Treating Psoriasis Based on Bioinformatics

目的运用生物信息学方法筛选银屑病炎症相关的特征基因并探索犀角地黄汤的干预机制。方法从GEO数据库中筛选包含银屑病皮损及正常对照的数据集。从GSEA数据库中获得炎症相关基因。使用limma包筛选出差异表达基因并与炎症相关基因取交集获取差异表达的炎症相关基因(differentially expressed inflammation-related genes,DEIRGs),并对DEIRGs进行基因本体论(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。通过加权基因共表达网络分析(weighted geneco-expression network analysis,WGCNA)和最小绝对值收敛和选择算子(least absolute shrinkage and selection operator,LASSO)回归筛选出银屑病炎症相关的特征基因,并进行受试者工作特征曲线(receiver operating characteristic curve,ROC)检验。检索TCMSP、TCMID数据库,筛选犀角地黄汤活性成分和靶点,与DEIRGs取交集得到有效作用成分和有效靶点。然后,通过Pubchem、PDB数据库获取相关结构文件,再利用swissdock数据库进行分子对接并计算结合能。结果本研究共筛选560个差异表达基因和20个DEIRGs。GO和KEGG富集分析共得到779条生物功能和37条通路。WGCNA分析共筛选出483个基因,与20个DEIRGs取交集得到9个银屑病核心炎症反应基因,通过LASSO回归筛选出6个与银屑病发病高度相关的炎症反应特征基因,分别为CXCL10、F3、NMI、P2RY2、RTP4和TPBG。ROC曲线显示各个基因的曲线下面积(area under curve,AUC)均>0.9,LASSO回归模型的AUC为1。将犀角地黄汤的中药成分采用网络药理学检索解析后发现赤芍中的活性成分鞣花酸(ellagic acid)可作用于CXCL8,芍药苷(paeoniflorin)可作用于IL-6;牡丹皮中的活性成分栎精(quercetin)可作用于CXCL8、IL-6、F3和CXCL10。结论CXCL10、F3、NMI、P2RY2、RTP4和TPBG可能是银屑病的炎症相关特征基因,预测犀角地黄汤中的赤芍、牡丹皮有作用于银屑病相关特征基因的成分,可为后续药物研究提供参考。

Objective To screen out the characteristic genes related to psoriasis inflammation and explore the intervention mechanism of Xijiao Dihuang decoction with Bioinformatics.Methods Screened the dataset including psoriasis skin lesions and normal controls from the GEO database,and obtained the gene related to psoriasis inflammation from the GSEA database.Limma was used to screen differentially expressed genes,which were intersected with inflammation-related genes to obtain differentially expressed inflammation-related genes(DEIRGs).GO and KEGG enrichment analysis were carried out for them.WGCNA and LASSO were used to screen out the characteristic genes related to psoriasis inflammation,and an ROC test was performed.Searched TCMSP and TCMID databases,and screened the active ingredients and targets of Xijiao Dihuang decoction,and intersected with DEIRGs to obtain effective ingredients and targets.Then,the related structure files were obtained through Pubchem and PDB databases,the molecular docking was obtained and the binding energy was calculated by Swissdock database.Results In this study,560 differentially expressed genes and 20 DEIRGs were screened.GO and KEGG enrichment analysis revealed that 779 biological functions and 37 pathways were enriched.A total of 483 genes were screened by WGCNA,and 9 core psoriasis inflammation genes were obtained by intersection with 20 DEIRGs.6 inflammatory characteristic genes highly related to psoriasis were screened by LASSO,namely CXCL10,F3,NMI,P2RY2,RTP4,and TPBG.The ROC curve showed that the AUC of each gene was greater than 0.9,and the AUC of LASSO was 1.The traditional Chinese medicine ingredients in Xijiao Dihuang decoction were searched and analyzed through network pharmacology.The results showed that the active component ellagic acid in Paeoniae Radix Rubra can act on CXCL8 and the active component paeoniflorin can act on IL-6.Additionally,the active component quercetin in the Moutan Cortex can act on CXCL8,IL-6,F3,and CXCL10.Conclusion CXCL10,F3,NMI,P2RY2,RTP4,and TPBG might be the characteristic genes related to psoriasis inflammation.Paeoniae Radix Rubra and Moutan in Xijiao Dihuang decoction were predicted to act on the characteristic genes related to psoriasis,which could provide a theoretical reference for future drug research.