基于网络药理学分析党参减轻大肠杆菌感染小鼠急性肺损伤的作用机制

Exploring the Mechanism of Codonopsis pilosula in Alleviation of Acute Lung Injury in Escherichia coli Infected Mice Based on Network Pharmacology

本研究以网络药理学和相关分子生物学试验相结合共同探究党参对小鼠急性肺损伤(acute lung injury,ALI)的保护作用机制。通过网络药理学相关数据库对党参的主要化学成分及主成分相关靶点进行挖掘。通过疾病相关数据库获取急性肺损伤的相关靶点。构建蛋白相互作用(PPI)网络,并对挖掘的数据进行GO分析和KEGG通路富集分析。结果表明,党参中的主要成分有8种化合物可作用于303个靶点;急性肺损伤相关靶点有1522个,党参与急性肺损伤相交靶点为119个,PPI网络包括MAPK,NF-κB和TLR4等总共103个核心靶点;GO功能富集分析显示,分子功能133条,生物学过程79条,细胞组分523条;KEGG富集分析显示相关通路132条。通过Western blot、ELISA和免疫荧光方法进行验证。试验结果表明,党参多糖(Codonopsis pilosula polysaccharide,CPPS)预处理可显著下调大肠杆菌诱导的巨噬细胞中MAPK和NF-κB炎症信号通路的激活,并可显著下调炎性细胞因子TNFα和IL-1β的分泌水平;此外小鼠体内试验表明党参多糖可显著下调小鼠肺中TNFα和IL-1β的产生,并可下调损伤相关因子HMGB1的表达从而降低大肠杆菌诱导的肺损伤。综上所述,党参可对急性肺损伤的疾病相关靶点通过多个通路及生物过程进行调控从而发挥对肺保护作用。

The network pharmacology and related molecular biology experiments were used to explore the protective mechanism of Codonopsis pilosula on acute lung injury(ALI).The main chemical components of Codonopsis radix and related targets were mined through the network pharmacology database.The related targets of ALI were obtained through disease-related databases.protein interaction(PPI)network was constructed,and GO analysis and KEGG pathway enrichment analysis were performed on the mined data.The results showed that 8 compounds in Codonopsis pilosula could act on 303 targets,1522 targets related to ALI,119 intersecting targets involved in ALI,103 targets in PPI network including MAPK,NF-κB and TLR4.GO functional enrichment analysis showed 133 molecular functions,79 biological processes and 523 cellular components,and KEGG showed 132 related pathways.The results were verified by Western blotting,ELISA and immunofluorescence.The results showed that Codonopsis pilosula polysaccharides pretreatment could down-regulate MAPK and NF-κB inflammatory signal pathways activation and TNFαand IL-1βsecretion in E.coli-induced macrophages.Furthermore,Codonopsis pilosula polysaccharide could down-regulate TNFαand IL-1βproduction,and down-regulate HMGB1 expression to reduce the lung injury in the E.coli-infected lungs of mice.In conclusion,Codonopsis pilosula could protect the lung by regulating disease-related targets of ALI through multiple pathways and biological processes.