基于网络药理学探讨大复方祛邪胶囊治疗结直肠癌的作用机制宋卓陈悦翟嘉威谷珊珊唐末龚璐天杨宇飞许云摘要目的：大復方祛邪胶囊是基于明代医家李中梓治疗积聚的名方——阴阳攻积丸研制而成，文章通过网络药理学方法挖掘其对结直肠癌的作用机制，为揭示经典名方阴阳攻积丸的临床价值和现代机制提供借鉴。方法：通过中药系统药理学数据库与分析平台（TCMSP）、中医药百科全书（ETCM）等数据库筛选祛邪胶囊的活性成分及靶点，通过SwissTargetPrediction靶标垂钓，取药物靶点的并集。通过TTD、OMIM、Drugbank和GeneCards数据库筛选结直肠癌的靶点，取并集。取药物靶点与疾病靶点的交集，并依据化合物的Degree值筛选，建立“中药-成分-靶点”数据库，依据核心靶点构建蛋白质-蛋白质相互作用（PPI）网络，进行基因本体（GO）功能和京都基因和基因组百科全书（KEGG）富集分析，与前期研究结果进行对比。结果：构建祛邪胶囊治疗结直肠癌的活性成分127个，靶向254个核心基因，核心基因的PPI网络包含248个节点，共有5个核心网络。富集分析显示祛邪胶囊可能主要通过调控RNA聚合酶的启动、DNA转录、翻译、蛋白的激活和增殖、凋亡、耐药、炎症反应等过程介导HIF-1α、PI3K/Akt、TNF、FoxO、Toll样受体等多个信号通路，其中凋亡、免疫方面的调节及FoxO信号通路得到本团队前期研究的验证。结论：祛邪胶囊治疗结直肠癌的作用机制与介导凋亡、免疫及FoxO信号通路方面有关，此外还可能调控HIF-1α、PI3K/Akt、TNF、Toll样受体等多个信号通路，体现了祛邪胶囊治疗结直肠癌成分多、调控通路和靶点复杂的特点，同时展现了古人“反激逆从”和“温阳通下”论治肿瘤的理论魅力和临床价值，为后续的深入研究提供指导。关键词结直肠癌;网络药理学;大复方;祛邪胶囊;阴阳攻积丸;经典名方;分子机制;中草药ExploringtheMechanismofaGreatPrescription（QuxieCapsule）inTreatmentofColorectalCancerBasedonNetworkPharmacologySONGZhuo1，CHENYue1，2，ZHAIJiawei1，2，GUShanshan1，TANGMo1，GONGLutian1，YANGYufei1，XUYun1（1XiyuanHospitalofChinaAcademyofChineseMedicalSciences，Beijing100091，China;2GraduateSchoolofBeijingUniversityofChineseMedicine，Beijing100029，China）AbstractObjective：DafufangQuxieCapsulesaredevelopedbasedonthefamousprescriptionYinyangGongjiPillsusedbythephysicianLIZhongziintheMingDynastytotreataccumulation.Theusesnetworkpharmacologytoexploreitsmechanismofactiononcolorectalcancer，inordertorevealtheclassicprescriptionYinYangGongjiPillsProvidereferenceforclinicalvalueandmodernmechanism.Methods：TCMSP，ETCMandotherdatabasesweresearchedtoestablishthedatabaseofactiveingredientsandtargetsofQuxieCapsules.FishingthroughtheSwissTargetPredictiontarget，wetooktheunionofthedrugtargets.ThroughTTD，OMIM，DrugbankandGeneCardsdatabases，wescreenedthetargetsofcolorectalcancerandtooktheunion.Wetooktheintersectionofdrugtargetanddiseasetarget，andscreenedaccordingtothedegreevalueofthecompound，establisheda“Chinesemedicine-component-target”database，constructedaPPInetworkbasedonthecoretarget，performedGOfunctionandKEGGenrichmentanalysis，andcomparedtheresultswithpreliminaryresearch.Results：ThefinaldataaboutQuxieCapsuleforthetreatmentofcolorectalcancerhad127activeingredientstargeting254coregenes.ThePPInetworkcontains248coregenes，andtherewere5subnetnetworksintotal.EnrichmentanalysisresultsshowedthatQuxieCapsulesmaymediateHIF1α，PI3K/AKT，TNF，FoxO，Toll-likereceptorsthroughprocessessuchastheinitiationofRNApolymerase，DNAtranscription，translation，proteinactivationandproliferation，apoptosis，drugresistance，andinflammation.Andmanyothersignalingpathways，amongwhichtheregulationofapoptosis，immunityandFoxOsignalingpathwayhavebeenverifiedbyourteam′...