【摘要】 目的 运用网络药理学探索“桃红四物汤”的主要活性成分，以及促进骨折愈合的作用机制。方法 利用中药系统药理数据库与分析平台（Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP）检索“桃红四物汤”（THSWT）中所有药物对应的活性成分，并筛选出其活性成分所对应的作用靶点。运用GeneCards数据库平台挖掘与骨折愈合（fracture healing,FH）相关作用靶点，构建“药物-疾病”共同靶点Venn图。利用Cytoscape 3.8.2软件，绘制“药物活性成分-靶点-疾病”的网络调控图，借助String 11.5构建蛋白-蛋白相互作用（protein-protein interaction,PPI）网络，获得PPI网络核心基因的邻接节点数目，再运用Cytoscape 3.8.2对PPI网络进行拓扑分析，最终获取核心基因。通过R语言包clusterProfiler进行基因本体（gene ontology,GO）功能注释和基于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，预测“桃红四物汤”对促进骨折愈合的作用机制。结果 研究预测得到“桃红四物汤”有效成分69个，涉及5 345个作用靶点。确定骨折愈合靶点2 383个，得到共同靶点基因140个，运用PPI分析确定ALB、AKT1、VEGFA、MMP2、MMP9、CASP3、JUN、MYC等是促进骨折愈合的核心靶点。富集分析GO条目2 258项（P <0.05）,KEGG信号通路151条（P <0.05），主要富集通路有PI3K-Akt信号通路、AGE-RAGE信号通路、IL-17信号通路等。结论 “桃红四物汤”可通过多靶点、多通路促进骨折愈合，为深入揭示其作用机制提供了研究方向，后续可继续通过体内外实验进一步验证靶点的有效性。更多还原

【Abstract】 Objective To explore the main active ingredients and mechanism of ″ Taohong Siwu Decoction″ promoting fracture healing using network pharmacology. Methods Using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) to search the active ingredients corresponding to all drugs in ″ Taohong Siwu Decoction″ （THSWT）,and screen the corresponding targets of the active ingredients.GeneCards database platform was used to mine the targets related to fracture healing(FH),and the Venn diagram of the ″ drug-disease″ common target was constructed. Cytoscape 3.8.2was used to draw the network regulation map of ″drug active component-target-disease″,and the protein-protein interaction(PPI)network was constructed with the help of String11.5 to obtain the number of adjacent nodes of core genes in the PPI network. Then Cytoscape 3.8.2 was used for topology analysis of the PPI network,and finally,the core genes were obtained. Functional annotation of gene ontology(GO)and pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes(KEGG)was taken using the R language package clusterProfiler to predict the mechanism of ″ Taohong Siwu Decoction″ on promoting fracture healing. Results 69 active components involving 5 345targets were predicted in ″Taohong Siwu Decoction″. 2 383 targets for fracture healing were identified,and 140 common target genes were obtained. The PPI analysis was used to identify ALB,AKT1,VEGFA,MMP2,MMP9,CASP3,JUN,and MYC as the core targets for promoting fracture healing. Enrichment analysis included 2 258 GO items(P <0. 05) and 151 KEGG signaling pathways(P < 0. 05). The main enrichment pathways were PI3K-Akt signaling pathway,AGE-RAGE signaling pathway,IL-17 signaling pathway,etc. Conclusion ″Taohong Siwu Decoction″ can promote fracture healing through multiple targets and pathways, which provides a research direction to further reveal its mechanism of action, and the effectiveness of the targets can be further verified through in vivo and in vitro experiments.更多还原