张元元 李旭 廖子君 王玉珍

摘要 目的：运用网络药理学的方法，探讨苦参治疗肝癌的作用机制。方法：通过中医药系统药理学数据库分析平台（TCMSP）筛选出苦参活性成分及作用靶点;在OMIM和Genecards中获取疾病靶点。通过R语言对基因进行匹配并绘制韦恩图;在String网站构建活性成分-蛋白质-蛋白质相互作用网络图;Cytoscape 3.6.1软件构建成分-靶点网络;通过R软件进行GO富集分析和KEGG通路富集分析。结果：共筛选出45个活性成分和176个潜在作用靶点;GO及KEGG功能富集显示苦参主要影响PI3K/Akt/mTOR通路及HIF-1a等信号通路。结论：苦参可能通过影响PI3K/Akt/mTOR通路及HIF-1a等信号通路，从而调控肝癌细胞侵袭及转移。

关键词 网络药理学;苦参;肝癌;机制;活性成分;靶点;富集分析;信号通路

Molecular Mechanism of Sophora Flavescens in the Treatment of Liver Cancer Based on Network Pharmacology

ZHANG Yuanyuan1，2，LI Xu2，LIAO Zijun2，WANG Yuzhen2

（1 Graduate Department，Xi′an Medical College，Xi′an 710068，China; 2 First Department

of Internal Medicine，Shaanxi Cancer Hospital，Xi′an 710061，China）

Abstract Objective：To explore the mechanism of Sophora flavescens in the treatment of liver cancer by means of network pharmacology.Methods：First，the active ingredients and targets of Sophora flavescens were screened through the TCMSP platform; then the disease targets were obtained from OMIM and Genecards.We matched genes through R language and draw a Venn diagram; then constructed an active ingredient-protein interaction network diagram on the String website; constructed a component-target network with Cytoscape 3.6.1 software; performed GO enrichment analysis and KEGG pathway enrichment analysis through R software.Results：A total of 45 active ingredients and 176 potential targets were screened; GO and KEGG function enrichment showed that Sophora flavescens mainly affected PI3K/Akt/mTOR pathway and HIF-1a signal pathways.Conclusion：Sophora flavescens may regulate the invasion and metastasis of liver cancer cells by affecting the PI3K/Akt/mTOR pathway and HIF-1a signaling pathways.

Keywords Network pharmacology; Sophora flavescens; Liver cancer; Mechanism; Active ingredients; Target; Enrichment analysis; Signal pathway

中圖分类号：R282;R735.7文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.05.013

肝癌发病率在所有恶性肿瘤中居于第6位，死亡率居第3位[1]。原发性肝癌属“积聚”范畴，对于本病的治疗侧重于补虚祛瘀、活血化瘀通络[2]。复方苦参注射液为临床常用辅助治疗肝癌药物。中医认为苦参主心腹结气，归肝胆经，而苦参具有软坚散结、止痛解郁、增强免疫功能等功效[3]。研究证实苦参成分中的苦参碱等活性成分具有抗肝癌细胞侵袭、迁移的作用[4]。本研究应用网络药理学的方法预测苦参治疗肝癌的多靶标及多通路的协同作用，进一步为肝癌的临床及相关基础研究提供参考。现报道如下。

1 资料与方法

1.1 参芪扶正注射液化学成分的收集及靶点预测 在中医药系统药理学数据库分析平台（Traditional Chinese Medicine Systems Pharmacology，TCMSP）中输入苦参进行成分与对应靶点的查询以及筛选每味中药可靠的成分信息。……