基于网络药理学及分子对接分析川芎嗪治疗脓毒症的作用机制

The Mechanism of Treating Sepsis by Ligustrazine Based on Network Pharmacology and Molecular Docking

目的:通过网络药理学及分子对接分析川芎嗪治疗脓毒症的机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、中药分子机制的生物信息学分析工具(a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine,BATMAN-TCM)、PharmMapper Server收集川芎嗪作用靶点,利用人类在线孟德尔遗传数据库(online Mendelian inheritance in man,OMIM)、人类基因的综合数据库(the human gene database,GENECARDS)、DRUGBANK ONLINE、靶点数据库(therapeutic target database,TTD)筛选脓毒症疾病相关靶点。使用STRING数据库进行川芎嗪治疗脓毒症作用靶点的蛋白互作网络(protein-protein interaction,PPI)分析,运用Cytoscape 3.7.1进行可视化,用其插件Cytohubba筛选关键靶点。利用DAVID 6.8数据库进行靶点GO功能富集分析和KEGG信号通路富集分析,利用Autodock Vina 1.1.2软件进行分子对接预测川芎嗪对脓毒症作用靶点的结合性。结果:筛选出川芎嗪作用靶点243个,川芎嗪治疗脓毒症作用靶点46个,关键靶点10个,信号通路10条。结论:川芎嗪治疗脓毒症具有多靶点、多通路作用的特点,其作用机制可能是通过调节免疫与凝血功能、保护血管内皮、抑菌、抗氧化、抗凋亡等多个机制治疗脓毒症。

Objective:To analyze the mechanism of ligustrazine in the treatment of sepsis through network pharmacology and molecular docking.Methods:The targets of lugustrazine were collected via TCMSP,BATMAN TCM and PharmMapper Server,sepsis-related targets were screened by using OMIM,GENECARDS,DRUGBANK ONLINE and TTD.PPI of ligustrazine in the treatment of sepsis was analyzed by using STRING database,visualization was performed by using Cytoscape 3.7.1,and its key targets were selected by using its plug-in Cytohubba.GO functional enrichment analysis and KEGG signaling pathway enrichment analysis of the targets were performed by using DAVID 6.8 database,and Autodock Vina 1.1.2 software was used to predict the binding of ligustrazine to sepsis targets by molecular docking.Results:All 243 targets of ligustrazine,46 targets of ligustrazine in the treatment of sepsis,10 key targets and 10 signaling pathways were screened.Conclusion:Ligustrazine in the treatment of sepsis shows the characteristics of multi-targets,multi-pathways,and its mecha nism of treating sepsis might be through many mechanisms of regulating immune and coagulation function,protecting vascular endothelium,inhibiting bacteria,oxidation resistance and anti-apoptosis.