麻杏石甘汤治疗新冠肺炎细胞因子风暴的网络药理学分析张云杨卉何轩辉吴广均李军摘要目的：用網络药理学方法探讨麻杏石甘汤成分、靶点、通路和生物学功能，阐明其治疗新型冠状病毒肺炎（COVID-19）细胞因子风暴的作用机制。方法：通过TCMSP、TCMID数据库以及文献报道，搜索麻杏石甘汤每味中药的成分和靶点，用Cytoscape软件构建和成分-靶点网络。用STRING搜素靶点的相关蛋白，并构建PPI网络。利用MECODE和ClusterOne聚类找出二者共同的关键靶点。利用Metascape和ClueGO对关键靶点进行通路和生物学功能富集分析。结果：麻杏石甘汤中麻黄有效成分6个、苦杏仁8个、石膏3个、生甘草92个。聚类分析得到67个关键靶点，其中IL-6和TNF是重要的核心靶点。麻杏石甘汤主要参与的分子通路和生物学功能与病毒感染和细胞因子免疫调节相关的是：人T细胞白血病病毒1型（TLV-1）感染;单纯疱疹病毒感染;TNF-R1信号通路和相关信号复合物;整合素1途径;白细胞介素信号;TH17细胞分化;炎性反应的调节;PI3K-Akt信号通路;白细胞介素-2介导的信号通路;免疫应答中细胞因子分泌的负调控;内皮屏障建立的调控;T细胞稳态增殖的调控。结论：麻杏石甘汤通过多成分、多靶点对机体的病毒感染和免疫炎性反应起到多方面的调控，包括促进TH细胞分化和T细胞稳态抑制病毒复制，负调控白细胞介素、TNF、整合素等免疫炎性反应递质消除细胞因子风暴。麻杏石甘汤针对COVID-19的病毒复制和细胞因子风暴具有显著的调节作用。关键词麻杏石甘汤;新型冠状病毒肺炎;细胞因子风暴;网络药理学AbstractObjective：Todiscussthecomposition，targets，pathwaysandbiologicalfunctionsofMaxingShigandecoctionandexploreitscurativemechanismofonCOVID-19cytokinestormbyusingnetworkpharmacology.Methods：ThecomponentsandtargetsofeachChineseherbalmedicineofMaxingShiganDecoctionweresearchedthroughTCMSPandTCMIDdatabase，andliteratures.ThecomponenttargetnetworkwasconstructedbyusingtheCytoscapesoftware.ThePPInetworkwasconstructedbysearchingtheproteinrelatedtothetargetinSTRINGdatabase.MECODEandClusterOneclusteringsoftwarewereusedtofindthecommonkeytargets.MetascapeandClueGosoftwarewereusedtoanalyzethepathwayandbiologicalfunctionenrichmentofkeytargets.Results：InMaxingShigandecoction，ephedrahas6effectivecomponents，bitterapricotseed8，gypsum3andliquoriceroot92.Amongthe67keytargetsobtainedbyclusteranalysis，IL6andTNFareimportantcoretargets.ThemainmolecularpathwaysandbiologicalfunctionsofMaxingShigandecoctionrelatedtovirusinfectionandcytokineimmunoregulationare：HTLV-1（humanT-cellleukemiavirustype1）infection;herpessimplexvirusinfection;TNF-R1signalpathwayandrelatedsignalcomplexes;integrin1pathway;interleukinsignal;Th17celldifferentiation;regulationofinflammatoryresponse;PI3KAktsignalingpathway;interleukin-2-mediatedsignalingpathway;negativeregulationofcytokinesecretioninimmuneresponse;regulationofendothelialbarrierestablishment;regulationofTcellhomeostaticproliferation.Conclusion：Basedonnetworkpharmacology，MaxingShigandecoctioncanregulatevirusinfectionandimmuneinflammatoryresponseinmanyaspectsthroughmulti-componentandmulti-target，includingpromotingTHcelldifferentiationandTcellhomeostaticproliferationtoinhibitvirusproliferation，andnegativelyregulatingimmuneinflammatoryfactorssuchasinterleukin，TNF，integrintoeliminatecytokinestorm.MaxingshigandecoctionhasasignificantregulatoryeffectsonCOVID-19virusreplicationandcytokinestorm.ThisstudyclarifiedthemechanismofthetreatmentofnewcoronarypneumoniawithLianhuangQingwen，JinhuaQinggan，QingfeiPaidudecoctionandotherprescriptionsbasedonMaxingShiganfromoneaspect，andprovidedascientificbasisforclinicalrationaldruguse.KeywordsMa...