目的 基于网络药理学方法探讨丹红化瘀口服液治疗深静脉血栓(deep vein thrombosis,DVT)的作用机制。方法 利用中药系统药理学技术平台数据库(TCMSP)获取丹红化瘀口服液的主要化学成分及作用靶点,利用Uniprot数据库对获取的作用靶点进行规范化处理;通过DisGeNet、GeneCards、OMIM、DrugBank数据库获取DVT相关靶点;利用Venny 2.1.0绘图网站构建Venn图,得到丹红化瘀口服液与DVT的交集靶点;应用String平台构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络;通过David数据库对交集靶点进行基因本体(gene ontology,GO)功能及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,使用微生信网站绘制结果气泡图,并利用KEGG Mapper平台制作通路机制图;相关结果采用Cytoscape 3.7.2软件进行可视化研究及网络拓扑结构分析。结果 经过数据库分析共筛选丹红化瘀口服液化学成分130个,潜在作用靶点268个,其中涉及DVT靶点136个。"中药-成分-疾病靶点"网络显示,槲皮素、木犀草素、山柰酚等是丹红化瘀口服液治疗DVT的主要活性成分,转录因子AP-1(transcription factor AP-1,JUN)、肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素-1β(interleukin-1β,IL-1β)、IL-6、信号传导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)等是丹红化瘀口服液治疗DVT的核心靶点。通过GO功能富集分析得到211条生物进程条目,124条分子功能条目,72条细胞成分条目。通过KEGG通路富集分析,得到3条与DVT相关的通路,即胞内磷脂酰肌醇3-激酶(phosphatidylinositol-3-kinase,PI3K)-蛋白激酶B(protein kinase B,Akt)通路、TNF信号通路、缺氧诱导因子-1(hypoxia-inducible factor-1,HIF-1)信号通路。结论 丹红化瘀口服液可通过多成分、多靶点和多通路发挥治疗DVT的作用,为拓宽其临床用途提供基础。

Objective To explore the mechanism of Danhong Huayu Oral Liquid (丹红化瘀口服液, DHOL) in the treatment of deep vein thrombosis (DVT) based on network pharmacology. Methods The main compounds and targets of DHOL were obtained with Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), then the acquired targets of DHOL were standardized by Uniprot database. Related targets of DVT were collected through databases of DisGeNet, GeneCards, OMIM and DrugBank. Then the intersection targets of DHOL-DVT were screened by constructing a Venn diagram with Venny 2.1.0 drawing website. Protein-protein interaction (PPI) network was constructed by String platform. Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed by DAVID database. The bubble charts were drawn by bioinformatics website, and diagrams of signaling pathway were built by KEGG Mapper platform. All of the related results were visualized by Cytoscape 3.7.2, and network topology feature analysis was made by Network Analyzer. Results A total of 130 chemical components in DHOL, and 268 potential targets including 136 DVT targets were screened out with database analyses. The result of "traditional Chinese medicine-compound-disease target" network showed that quercetin, luteolin, kaempferol were main active ingredients of DHOL for the treatment of DVT, transcription factor AP-1 (JUN), tumor necrosis factor (TNF), interleukin-1β (IL-1β), IL-6, signal transducer and activator of transcription 3 (STAT3) were core targets. Furthermore, 211 biological process terms, 124 molecular functional terms and 72 cellular component terms were obtained with GO function enrichment analysis. Moreover, three relative pathways of DVT including phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, TNF signaling pathway and hypoxia-inducible factor-1 (HIF-1) signaling pathway were obtained with KEGG pathway enrichment analysis. Conclusion DHOL plays a role in the treatment of DVT through multi-component, multi-target and multi-channel, which provides a basis for broadening its clinical application.

R285.5

广州市科技计划项目（202002030108）