基于网络药理学探讨补骨丸治疗绝经后骨质疏松症的分子作用机制  

Exploring the molecular mechanism of Bugu Wan on postmenopausal osteoporosis based on network pharmacology

作　　者：廖国平 胡军平 杨峰 尹新生 欧礼 尹书东 胡建华 陈一帆 LIAO Guoping

机构地区：[1]湖南省常宁市中医医院,湖南常宁421500

出　　处：《中医临床研究》2022年第2期10-14,共5页Clinical Journal Of Chinese Medicine

基　　金：湖南省中医药科研计划项目重点课题(201742);中国特色示范骨伤科建设项目;湖南省中医药重点研究室(詹氏正骨重点研究室);湖南省“十三五”省级中医重点专科建设项目(中药学)。

摘　　要：目的:基于网络药理学方法探讨补骨丸治疗绝经后骨质疏松症(Postmenopausal Osteoporosis,PMOP)的潜在分子作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)检索补骨丸中14味药中含有的活性成分,筛选有效活性成分及其潜在作用靶点;运用GeneCards数据库获取与PMOP相关的靶标基因,采用Cytoscape 3.6.3软件构建“药物-活性成分-靶点基因”网络;基于网络中的靶标基因,使用String在线平台进行蛋白质-蛋白质相互作用网络分析,采用Metascape数据库进行基因本体论(GO)及京都基因与基因组百科全书(KEGG)通路富集分析。结果:通过筛选共得到118个有效活性成分,102个药物靶点,54个PMOP相关且药物作用的靶标基因,54个蛋白质-蛋白质相互作用网络蛋白,23个网络核心蛋白,关键蛋白涉及白细胞介素(Interleukin,IL)-6、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、半胱氨酸天冬氨酸蛋白酶3(Caspase 3,CASP3)、丝裂原活化蛋白激酶8(Mitogen-activated Protein Kinase 8,MAPK8)、前表皮生长因子(Pro-epidermal Growth Factor,EGF)、RELA癌基因(RELA Proto-Oncogene,NF-KB Subunit,RELA)和受体酪氨酸蛋白激酶erbB-2(Receptor Tyrosine Protein Kinase erbB-2,ERBB2)等;获得280条GO生物过程(BP)和70条相关信号通路,涉及肿瘤坏死因子信号通路、细胞凋亡、磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)信号通路、p53信号通路、c型凝集素受体信号通路、Th17细胞分化、催乳素信号通路、IL-17信号通路、内分泌抵抗、雌激素信号通路、鞘脂类信号通路和Toll样受体信号通路等。结论:补骨丸可能通过调节雌激素、骨代谢,促进成骨细胞生成和抑制破骨细胞分化等治疗PMOP,是多成分、多靶点、多通路相互作用的结果,为补骨丸治疗PMOP提供了理论支持。Objective:To explore the molecular mechanism of Bugu Wan(补骨丸)on postmenopausal osteoporosis based on network pharmacology.Methods:In TCMSP,the active ingredients contained in 14 Chinese medicines in Bugu Wan were searched,and the effectively active ingredients and their potential targets were screened out.The target genes related to PMOP was obtained from GeneCards database,and the“drug-active ingredient-target gene”network was constructed by Cytoscape 3.6.1 software.Based on the target genes,the PPI network was analyzed by String online platform.The GO enrichment analysis and KEGG enrichment analysis were conducted by Metascape database.Results:After screening,118 effectively active ingredients and 102 drug targets for the treatment of PMOP were obtained.A total of 54 targets genes were related to PMOP and were affected by medicines.There were 54 PPI network proteins,23 proteins were defined as the PPI network core nodes,and the key proteins included IL-6,VEGFA,CASP3,MAPK8,EGF,RELA,ERBB2,etc..After enrichment analysis,280 biological processes of GO and 70 KEGG signal pathways were obtained,including TNF signaling pathway,apoptosis,PI3K-Akt signaling pathway,p53 signaling pathway,c-type lectin receptor signaling pathway,Th17 cell differentiation,prolactin signaling pathway,IL-17 signaling pathway,endocrine resistance,estrogen signaling pathway,sphingolipid signaling pathway,Toll-like receptor signaling pathway,etc..Conclusion:Bugu Wan may treat PMOP by regulating estrogen and bone metabolism,promoting osteoblast formation,and inhitbiting osteoclast differentiation,which is the result of multi-component,multi-target and multi-channel interaction,providing theoretical support for treating PMOP with Bugu Wan.

关 键 词：补骨丸 网络药理学 绝经后骨质疏松症 信号通路 

分 类 号：R336[医药卫生—人体生理学]