基于网络药理学探讨四逆散治疗慢性乙型肝炎的作用机制

Study on mechanisms of Sini powder in the treatment of chronic hepatitis B based on network pharmacology

目的:基于网络药理学探索四逆散治疗慢性乙型肝炎(CHB)的相关机制。方法:利用中药系统药理学分析平台(TCMSP)、Swiss Target Prediction、GeneCards等数据库获得四逆散的有效成分预测靶点和CHB的治疗作用靶点,运用Cytoscape将交集靶点绘制成药物有效成分-靶点网络图,采用String数据库构建PPI蛋白互作网络,运用Cytoscape软件MCODE插件进行模块化分析,运用R软件及clusterProfiler对交集靶点进行GO和KEGG富集分析。结果:筛选出四逆散139个有效成分及296个对应靶点。药物有效成分-靶点网络图中共包含423个节点,有效成分和靶点相互作用关系为1840条边,靶点STAT3、JUN与四逆散有效成分相互作用最为密切;PPI网络共包含257个节点,1241条连接;GO分析显示,四逆散治疗CHB与内肽酶活性、酰胺结合、肽结合、泛素化蛋白连接酶结合、氧化还原酶活性等生物功能相关;KEGG分析显示,四逆散治疗CHB与乙型肝炎、白细胞介素-17信号通路、细胞凋亡、Toll样受体信号通路、Th17细胞分化等通路有关。结论:四逆散主要通过调控免疫应答状态抑制HBV复制、转录来治疗CHB,同时具有抑制炎症反应、保护肝脏的作用。

Objective:To explore the biological mechanism of Sini Powder in the treatment of chronic hepatitis B(CHB)based on network pharmacology.Methods:predictive targets of the active ingredients of Sini Powder and the therapeutic targets of CHB were obtained by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Swiss Target Prediction,GeneCards and other databases.After finding out the intersection targets,the drug active ingredients-target network diagram was drew by Cytoscape.PPI protein interactions Network was constructed by String database,Cytoscape software MCODE plug-in was used for modular analysis.R and clusterProfiler were used to carry out GO and KEGG enrichment analysis on the intersection target.Results:139 active components and 296 targets of Sini Powder were selected.A total of 423 nodes were included in the drug active component-target network diagram.There were 1840 edges between the active components and the targets.The targets STAT3 and JUN interacted most closely with the active ingredients of Sini Powder.PPI network consisted of 257 nodes with 1241 connections.GO analysis showed that Sini Powder treatment of CHB was related to endopeptidase activity,amide binding,peptide binding,ubiquitin-like protein ligase binding,oxidoreductase activity and other biological functions.KEGG analysis showed that Sini Powder treatment of CHB was associated with hepatitis B,IL-17 signaling pathway,cell apoptosis,Toll like receptor signaling pathway,Th17 cell differentiation and other pathways.Conclusion:Sini Powder mainly inhibits HBV replication and transcription to treat CHB by regulating the immune response,as well as inhibiting inflammation and protecting the liver.