刘寰宇 王焱冰 杨涛 崔人匀 安炯俊 陈健 郝力争 李忠

摘要 目的：探究芪甲扶正方治療肺腺癌相关性疲乏的作用机制。方法：基于中药系统药理学数据库与分析平台（TCMSP）、中医药综合数据库（TCMID）、Pubchem、Swiss Target Prediction等数据库收集芪甲扶正方有效成分及作用靶点;通过GeneCards、OMIM等数据库获取“肺腺癌相关性疲乏”相关靶基因;将药物靶点映射到疾病靶点集合上，获取交集基因;使用String构建蛋白质-蛋白质相互作用（PPI）网络;通过Cytoscape构建药物-成分-靶点调控网络;利用DAVID数据库对芪甲扶正方治疗肺腺癌相关性疲乏的靶点进行基因本体（GO）富集分析和京都基因和基因组百科全书（KEGG）富集分析;运用Genebank数据库分析交集基因的组织器官定位;利用AutoDock Vina_1.1.2分析主要活性成分和关键靶点的结合能力，并使用PYMOL软件将对接结果进行可视化展示。结果：调控网络共包含9味中药、108种活性成分、87个靶基因;和CASP3、VEGFA、EGFR、MYC、IL-6;KEGG富集分析涉及PI3K-AKT、p53、TNF、MAPK、ErbB、Ras、FoxO等通路;关键基因主要分布在肺、红细胞、T细胞、B细胞;分子对接结果表明EGFR与木犀草素、IL-6、MAKP3与β-谷甾醇、MAKP8与鞣花酸具有较强的结合能力。结论：芪甲扶正方活性成分鞣花酸、β-谷甾醇等，可能通过作用于EGFR、IL-6、MAKP3、MAKP8等靶点，进而通过调节PI3K-AKT通路发挥对肺腺癌相关性疲乏的治疗作用。

关键词 肺腺癌;癌因性疲乏;芪甲扶正方;网络药理学;分子对接;鞣花酸;IL6;PI3K-AKT

Abstract Objective：To explore the action mechanism of Qijia Fuzheng Formula in the treatment of fatigue-related lung adenocarcinoma.Methods：Based on databases such as TCMSP，TCMID，Pubchem，Swiss Target Prediction，etc.，the active ingredients and targets of Qijia Fuzheng Formula were collected; relevant target genes of “pulmonary adenocarcinoma-related fatigue” from databases such as GeneCards and OMIM were obtained; drug targets were mapped to diseases target set.The intersection genes on the target set were obtained; String was used to construct a protein-protein interaction（PPI） network; Cytoscape was used to construct a drug-component-target regulatory network;DAVID database was used to enrich（GO，KEGG） analysis of the targets of Qijiafuzheng Formula in the treatment of lung adenocarcinoma-related fatigue; Genebank database was used to analyze the tissue and organ location of intersection genes; AutoDock Vina_1.1.2 was used to analyze the main active ingredients and key binding ability of the target，and PYMOL was used software to visualize the docking results.Results：The drug-compound-target network consisted of 9 drugs，108 compounds and 87 targets; and CASP3，VEGFA，EGFR，MYC，IL-6; KEGG enrichment analysis involved PI3K-AKT，p53，TNF，MAPK，ErbB，Ras，FoxO and other pathways; key genes were mainly distributed in lungs，red blood cells，T cells，B cells; molecular docking results showed that EGFR and luteolin，IL-6，MAKP3 and β-sitosterol，MAKP8 and ellagic acid had strong binding ability.Conclusion：The active ingredients of Qijia Fuzheng Formula，such as ellagic acid and β-sitosterol，may act on EGFR，IL-6，MAKP3，MAKP8 and other targets，and then play a role in the treatment of lung adenocarcinoma-related fatigue by regulating the PI3K-AKT pathway effect.

Keywords Lung adenocarcinoma; Cancer related fatigue; Qijia Fuzheng Formula; Network pharmacology; Molecular docking; Luteolin; IL6; PI3K-AKT

中圖分类号：R285文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.11.008

癌症相关性疲劳（Cancer Related Fatigue，CRF）是80%肿瘤患者正在或已经经历过的虚弱症状[1]，具有多维度、多阶段、不可缓解等特点，近年来随着肿瘤治疗理念由传统的对抗治疗到姑息治疗理念的转变，癌性疲乏已经引起越来越多肿瘤研究者的关注[2]。……