基于网络药理学及实验验证探讨三七治疗骨折的作用机制  

Exploration on the Mechanism of the Treatment of Fracture by Panax Notoginseng Based on Network Pharmacology and Experimental Validation

作　　者：熊贤梅 马立琼 李世杰 冯俊铭 王钟庆 蒲彬 杨柏霖 高怡加[2] XIONG Xianmei;MA Liqiong;LI Shijie;FENG Junming;WANG Zhongqing;PU Bin;YANG Bailin;GAO Yijia(The First Clinical Medical School of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,,China)

机构地区：[1]广州中医大学第一临床医学院,广东广州510405 [2]广州中医药大学第一附属医院,广东广州510405

出　　处：《中药新药与临床药理》2022年第12期1684-1693,共10页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广东省自然科学基金项目(2018A030313369);黄枫全国名老中医药专家传承工作室建设项目。

摘　　要：目的 基于网络药理学方法预测三七治疗骨折的作用机制,并通过动物实验进行验证。方法 通过中药系统药理学数据库分析平台(TCMSP)、文献报道以及Swiss Target Prediction筛选三七主要活性成分及靶点,利用GeneCards数据库收集骨折靶点,再使用String数据库和Cystoscope 3.7.2软件构建蛋白相互作用(PPI)网络,同时筛选核心靶点,建立“三七-活性成分-骨折-靶点”网络,并对潜在核心靶点进行基因本体(gene ontology,GO)功能富集分析和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。最后通过动物实验对三七治疗骨折进行疗效分析,对部分靶点进行验证。结果 共筛选获得三七活性成分20个及其相应靶点356个,骨折靶点5 235个,两者交集靶点205个。三七治疗骨折潜在核心靶点包括蛋白激酶(AKT1)、白细胞介素6(IL-6)、血管内皮生长因子A(VEGFA)、表皮生长因子受体(EGFR)、信号转导与转录激活因子3(STAT3)、表皮生长因子(EGF)、丝裂原活化蛋白激酶1(MAPK1)等。通路富集分析中与三七治疗骨折密切相关的通路主要涉及PI3K-Akt信号通路(PI3K-Akt signaling pathway)、缺氧诱导因子1信号通路(HIF-1 signaling pathway)、Ras信号通路(Ras signaling pathway)、丝裂原活化蛋白激酶信号通路(MAPK signaling pathway)。动物实验结果显示三七可以促进桡骨骨析模型兔的骨折愈合,分别提高EGFR、VEGFA、EGF和降低IL-6的水平。结论 该研究以网络药理学分析三七治疗骨折的作用机制并通过动物实验加以验证,为三七在临床治疗骨折研究提供了实验依据。Objective To predict the mechanism of action of Panax notoginseng in the treatment of fractures based on a network pharmacology approach, and to provide preliminary evidence through animal experiments. Methods The main active ingredients and targets of Panax notoginseng were screened by TCMSP,literature reports and Swiss Target Prediction,and the fracture targets were collected by GeneCards database. Then,using the String database and Cystoscope 3.7.2 software,we constructed the protein-protein interaction(PPI)network and screened the core targets to establish the "Panax notoginseng-active ingredient-fracture-target" network. The potential core targets were subjected to gene ontology(GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis. Finally,the therapeutic effect of Panax notoginseng on fracture was observed by animal experiments and some targets were verified. Results A total of 20 active ingredients of Panax notoginseng and 356 corresponding targets were screened,and 5 235 fracture targets and 205 intersecting targets were obtained.The potential core targets of Panax notoginseng for fracture treatment included protein kinase(AKT1),interleukin 6(IL-6), vascular endothelial growth factor A(VEGFA), epidermal growth factor receptor(EGFR), signal transducer and activator of transcription 3(STAT3), epidermal growth factor(EGF), mitogen-activated protein kinase 1(MAPK1),etc. The pathways closely related to fracture treatment with Panax notoginseng in the pathway enrichment analysis mainly involved PI3K-Akt signaling pathway,HIF-1 signaling pathway,Ras signaling pathway,and MAPK signaling pathway. Animal experiments showed that Panax notoginseng could promote fracture healing in rabbit model of radius fracture, increase EGFR, VEGFA, and EGF and decrease IL-6 levels, respectively.Conclusion This study analyzed the mechanism of action of Panax notoginseng in the treatment of fractures through network pharmacology and verified results through animal experiment

关 键 词：三七 骨折 网络药理学 实验验证 作用机制 兔 

分 类 号：R285.5[医药卫生—中药学]