基于网络药理学探讨益气补肺颗粒对肺癌的免疫调节机制  

Study on the immunomodulatory mechanism of Yiqi Bufei granule on lung cancer based on network pharmacology

作　　者：戴菲菲[1] 孔红武[1] 谢柏胜 DAI Feifei;KONG Hongwu;XIE Baisheng(Department of Cardiothoracic Surgery,Hangzhou Hospital of Traditional Chinese Medicine,Hangzhou 310007,Zhejiang,China)

机构地区：[1]杭州市中医院胸心外科,浙江杭州310007

出　　处：《中国现代医生》2023年第15期58-63,共6页China Modern Doctor

基　　金：浙江省中医药科技计划项目(2021ZQ063)。

摘　　要：目的利用网络药理学方法探讨益气补肺颗粒对肺癌的免疫调节机制。方法应用中药系统药理学数据库分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、公共化合物数据库(PubChem)、药物靶点预测数据库(Swiss Target Prediction)及人类基因数据库(the Human Gene Database,GenCards)分别获得药物成分、药物潜在靶点和肺癌相关靶点,将二者交集靶点通过String数据平台进行药物-疾病蛋白质互作网络构建,进而利用Cytoscape软件筛选出关键药物成分和核心靶点。通过Webgestalt数据平台进行基因本体(gene ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析;运用AutoDock进行分子对接。结果益气补肺颗粒含有潜在活性成分129个,主要成分包括3-甲氧基光甘草定、甘草酚、菜豆醇、7-甲氧基-2-甲基异黄酮、豆甾醇。调节肺癌相关免疫功能的潜在靶点137个,核心靶点主要有信号转导及转录激活蛋白3(signal transduction and activator of transcription 3,STAT3)、丝氨酸/苏氨酸蛋白激酶1(rac-alpha serine/threonine-protein kinase,AKT1)、酪氨酸蛋白激酶(tyrosine protein kinase,TPK)、丝裂原活化蛋白激酶3(mitogen-activated protein kinase3,MAPK3)、热休克蛋白90α家族A类成员1[heat shock protein 90-kDa alpha(cytosolic),class A member 1,HSP90AA1]。GO富集分析结果显示核心靶点主要与炎症反应、免疫系统调节、蛋白质磷酸化等有关;KEGG信号通路主要包括C型凝集素受体(c-type lectin receptor,CLR)信号通路、血管内皮生长因子(vascular endothelial growth factor,VEGF)信号通路、Th17细胞分化等。分子对接结果显示5个关键成分与5个核心靶点均有较好的结合活性。结论益气补肺颗粒可通过甘草、天冬、当归、人参中的多种活性成分、多靶点作用,并通过影响CLR信号通路、VEGF信号通路、Th17细�Objective To explore the mechanism of Yiqi Bufei granule in regulating immune function of lung cancer by network pharmacology.Methods Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),PubChem,Swiss Target Prediction and the human gene database(GenCards)were used to obtain drug components,potential drug targets and lung cancer related targets,respectively.The intersection targets of the two were used to construct drug-disease protein interaction network through String data platform.CytoScape software was used to screen out key drug components and core targets.Gene ontology(GO)enrichment analysis and Kyoto Eencyclopedia of Genes and Genomes(KEGG)pathway analysis were analyzed by Webgestalt data platform.Molecular docking was performed using AutoDock.Results Yiqi Bufei granule contained 129 potential active ingredients,included 3-methoxy-glabridin,glycyrol,phaseol,7-methoxy-2-methyl isoflavone,and stigmasterol.There were 137 potential targets for regulating lung cancer-related immune function,and the core targets mainly included signal transduction and activator of transcription 3(STAT3),proteinkinase(AKT1),tyrosine protein kinase(TPK),mitogen-activated protein kinase3(MAPK3)and heat shock protein 90-kDa alpha(cytosolic),class A member 1(HSP90AA1).GO enrichment analysis showed that the core targets were mainly related to inflammatory response,immune system regulation,protein phosphorylation,etc.KEGG pathway mainly included c-type lectin receptor(CLR)signaling pathway,vascular endothelial growth factor(VEGF)signaling pathway,Th17 cell differentiation and so on.The results of molecular docking showed that the five key components had good binding activities with the five core targets.Conclusion Yiqi Bufei granule may have multiple active ingredients and targets in licorice,tiandong,angelica,ginseng,and may also improve the immune function of lung cancer patients by affecting multiple pathways such as CLR signaling pathway,VEGF signaling pathway,and Th17 cell differentiation.

关 键 词：肺癌 免疫功能 益气补肺颗粒 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]