基于网络药理学的桃红四物汤治疗股骨颈骨折初期的物质基础及实验验证  

Material Basis and Experimental Verification of Taohong Siwu Decoction Against Femoral Neck Fracture in Early Phase Based on Network Pharmacology

作　　者：杨卓 熊辉[2] 沈浮 袁博[3] 方萍 齐新宇[2] 段建辉 贺渊哲 YANG Zhuo;XIONG Hui;SHEN Fu;YUAN Bo;FANG Ping;QI Xinyu;DUAN Jianhui;HE Yuanzhe(Changde First Hospital of Traditional Chinese Medicine,Changde 415000,China;Hunan University of Chinese Medicine,Changsha 410208,China;The First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China)

机构地区：[1]常德市第一中医医院,常德415000 [2]湖南中医药大学,长沙410208 [3]湖南中医药大学第一附属医院,长沙410007

出　　处：《世界中医药》2022年第24期3443-3448,共6页World Chinese Medicine

基　　金：国家自然科学基金项目(81874478);湖南省教育厅科学研究项目(21C0225);湖南省教育厅科学研究项目(22C0187)。

摘　　要：目的:基于网络药理学的方法,对桃红四物汤主要活性成分进行筛选,并收集相关靶点,探索其治疗股骨颈骨折初期的可能分子机制。方法:检索中药系统药理学数据库与分析平台(TCMSP)获得桃红四物汤活性成分的干预靶点,再与GeneCards数据库中股骨颈骨折基因靶点相映射得到交集靶点;使用Cytoscape 3.7.0软件构建“活性成分-靶点”网络;利用String数据库得到交集靶点相互作用网络;使用R语言联合数据包进行桃红四物汤潜在靶点的基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析,再在动物层面验证方剂的有效性。结果:共筛选出桃红四物汤治疗股骨颈骨折关键活性成分主要有槲皮素、山柰酚、木犀草素、黄芩素、β-胡萝卜素等,潜在靶点PTGS2、NCOA2、PTGS1、HSP90AA1、PGR等,股骨颈与桃红四物汤交集靶点共121个,其生物过程与PI3K-AKT、核因子κB、IL-17及TNF信号通路等相关信号通路关系密切。动物实验显示桃红四物汤加减可促进股骨骨折早期愈合。结论:桃红四物汤有效促进骨折愈合,网络药理学表明桃红四物汤中通过AKT1、MAPK-8、IL-6等关键靶蛋白结合多条通路治疗股骨颈骨折,为临床治疗提供理论依据。Objective:To screen the main active ingredients of Taohong Siwu Decoction and collect related targets to explore its possible molecular mechanism in the treatment of femoral neck fracture in early phase based on network pharmacology.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was searched to obtain the intervention targets of the active ingredients of Taohong Siwu Decoction,which were then mapped with the gene targets of femoral neck fracture in GeneCards to obtain the intersection targets.Cytoscape 3.7.0 was used to construct the“active ingredient-target”network,and the interaction network of the intersection targets was built by String.R language package was employed to perform the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of the potential targets of Taohong Siwu Decoction.Results:The key active ingredients of Taohong Siwu Decoction in the treatment of femoral neck fracture were quercetin,kaempferol,luteolin,baicalein,β-carotene,etc.,acting on the potential targets of PTGS2,NCOA2,PTGS1,HSP90AA1,PGR,etc.There were 121 intersection targets of femoral neck and Taohong Siwu Decoction,and the biological processes were closely related to PI3K-Akt,NF-κB,IL-17,and TNF signaling pathways.Animal experiment indicated that modified Taohong Siwu Decoction promoted the early healing of femoral fracture.Conclusion:Taohong Siwu Decoction facilitates the fracture healing,and network pharmacology reveals that the prescription treats femoral neck fracture through AKT1,MAPK-8,IL-6 and other key target proteins combined with multiple pathways,providing a theoretical basis for clinical treatment.

关 键 词：桃红四物汤 网络药理学 股骨颈骨折 物质基础 靶点 通路 

分 类 号：R285[医药卫生—中药学]