摘要
【目的】基于网络药理学方法探讨三七对骨愈合的作用机制。【方法】通过中药系统药理学技术平台(TCMSP)获取三七的主要化学成分及其对应的作用靶点;借助人类基因数据库(GeneCards)获取骨愈合相关靶标基因,与三七作用靶点取交集后获得三七—骨愈合的交集靶点。通过Cytoscape 3.7.1软件构建中药调控网络并进行可视化展示;通过STRING在线数据库构建蛋白相互作用(PPI)网络。利用DAVID数据库进行交集基因的基因本体论(GO)功能富集分析及基于京都基因与基因组百科全书(KEGG)通路富集分析。【结果】三七作用于骨愈合的化学成分有7个,相关靶点70个,关键有效成分4个,关键靶点68个。GO分析结果显示,三七—骨愈合的交集基因的生物功能主要涉及对雌二醇的反应、RNA聚合酶II启动子转录的正调控、DNA模板转录的正调控等生物过程,细胞质基质、细胞外间隙、核质等细胞组成;酶结合、相同的蛋白结合、转录因子结合等分子功能。KEGG通路富集结果显示,三七—骨愈合的交集基因的通路主要包括人类疾病通路(如肿瘤疾病通路、乙型肝炎等)、环境信息处理通路[如磷脂酰肌醇3-激酶/蛋白激酶B(PI3K-Akt)信号通路、缺氧诱导因子1(HIF-1)信号通路等]、有机系统通路(如甲状腺激素信号通路、催乳激素信号通路等)、细胞过程通路(如细胞局部粘附、p53信号通路等)。【结论】三七调节骨愈合的作用机制呈多成分、多靶点、多通路特点,主要通过肿瘤疾病通路、PI3K-Akt信号通路、甲状腺激素信号通路、细胞局部粘附等多方面的途径发挥调节骨愈合的作用。
Objective To explore the effect mechanism of Radix Notoginseng for bone healing based on network pharmacology. Methods The main chemical components and corresponding targets of Radix Notoginseng were obtained from the platform of Traditional Chinese Medicine(TCM)Systems Pharmacology(TCMSP), and the target genes related with bone healing were obtained from human gene database(GeneCards), and then the intersecting targets between Radix Notoginseng and bone healing were obtained. The TCM regulation network was constructed and displayed visually by Cytoscape3.7.1 software,and the protein-protein interaction(PPI)network was constructed by STRING online database. Finally,DAVID database was used to carry out the gene ontology(GO)functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis for the intersecting targets. Results There were 7 chemical components,70 related targets,4 key active components and 68 key targets of Radix Notoginseng acting on bone healing. The Go analysis showed that the biological functions of the potential genes of Radix Notoginseng acting on bone healing were mainly involved biological processes(such as response to estradiol,positive regulation of transcription from RNA polymerase II promoter,positive regulation of DNA-templated transcription),cellular components(such as cytosol,extracellular space, nucleoplasm), molecular functions(such as enzyme binding, identical protein binding, transcription factor binding). The KEGG analysis showed that the intersection gene pathways of Radix Notoginseng-bone healing included human disease pathways(such as pathways in cancer,hepatitis B,etc.),environmental information processing pathways[such as phosphatidylinositide 3-kinases/protein kinase B(PI3 K-Akt)signaling pathway,hypoxia inducible factor 1(HIF-1)signaling pathway,etc.],organic system pathways(such as thyroid hormone signaling pathway,prolactin signaling pathway,etc.),and cell process pathways(such as focal adhesion,p53 signaling pathway, etc.). Conclusion The mechanism of Radix Notoginseng for regulating bone healing is characterized by multiple components,targets and pathways,which plays a role in regulating bone healing mainly through the pathways in cancer,PI3 K-Akt signaling pathway,thyroid hormone signaling pathway and cell focal adhesion.
作者
吴文正
郑晓辉
高怡加
欧阳崇志
黄敏玲
杨锐敏
WU Wen-Zheng;ZHENG Xiao-Hui;GAO Yi-Jia;OUYANG Chong-Zhi;HUANG Min-Ling;YNAG Rui-Min(The First Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China)
出处
《广州中医药大学学报》
CAS
2020年第8期1561-1567,共7页
Journal of Guangzhou University of Traditional Chinese Medicine
基金
广东省自然科学基金资助项目(编号:2018A030313369)
广东省中医药局科研项目(编号:20181084)。