中国骨质疏松杂志

基于网络药理学的济生肾气丸治疗骨质疏松症的分子机制研究

Study on the molecular mechanism of Jisheng Shenqi pill for the treatment of osteoporosis based on network pharmacology

DOI：10.3969/j.issn.1006-7108.2020.10.012

中文关键词: 中医中药济生肾气丸骨质疏松症网络药理学信号通路作用机制

英文关键词:traditional Chinese medicine Jisheng Shenqi pill osteoporosis network pharmacology signal pathway mechanism of action

基金项目:国家重点研发计划——骨质疏松高风险人群中医“治未病”干预技术示范研究（2018YFC1704703）

作者	单位
傅繁誉1 黄泽青2 孙继高2 王荣田3 叶恒力1 陈卫衡3*	1.贵州中医药大学，贵州贵阳 550002 2.中国中医科学院望京医院，北京 100102 3.北京中医药大学第三附属医院，北京 100029

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中文摘要:

目的应用网络药理学分析技术研究济生肾气丸治疗骨质疏松症（OP）的分子作用机制。方法通过TCMSP数据库查询并筛选出济生肾气丸全方共10味中药的活性成分及有效靶点；检索Comparative Toxicogenomics Database（CTD）、GeneCards、Online Mendelian Inheritance in Man（OMIM）三大疾病靶点数据库查询骨质疏松症相关靶点；利用Venny 2.1统计复方与疾病的交集靶点，并绘制Venn图。利用Cytoscape 3.6软件，绘制活性成分-交集靶点网络图。将交集靶点导入String数据库后获得的数据经Cytoscape的CytoHubba插件构建蛋白互作网络图。通过DAVID数据库进行基因功能GO分析和KEGG通路富集分析，并利用R-studio软件进行气泡图绘制。利用Cytoscape绘制核心靶点与KEGG通路的网络图。结果济生肾气丸中共得到63个活性成分，预测出211个相关靶点；经过三大数据库共检索出OP相关靶点3 126个；复方与疾病交集靶点132个。通过Cytoscape构建交集基因蛋白互作网络图与核心靶点-通路网络图，按照连接节点（degree）大小排列显示济生肾气丸主要通过作用于AKT1、MAPK1、IL6、MAPK8、JUN、VEGFA等靶基因及调控肿瘤坏死因子信号通路、白细胞介素17信号通路、AGE-RAGE信号通路、流体剪切应力和动脉粥样硬化信号通路等发挥治疗OP的作用。结论济生肾气丸治疗OP具有多成分、多靶点、多系统的特点，其作用机制可能通过抑制破骨细胞的生成、刺激成骨细胞的活性、调节骨代谢平衡、降低炎症反应等途径有关。

英文摘要:

Objective To study the molecular mechanism of Jisheng Shenqi Pill in treating osteoporosis (OP) by applying network pharmacological analysis technology. Methods The TCMSP database was used to query and screen out the active ingredients and effective targets of a total of 10 traditional Chinese medicines of Jisheng Shenqi Pills. The three major disease targets were retrieved: Comparative Toxicogenomics Database (CTD), GeneCards and Online Mendelian Inheritance in Man (OMIM) Point database to query osteoporosis-related targets; use Venny 2.1 to count intersection targets of compound and disease, and draw Venn diagram. Using Cytoscape 3.6 software, draw the active ingredient-intersection target network diagram. The data obtained after the intersection targets were imported into the String database was used to construct a protein interaction network map by Cytoscape's CytoHubba plug-in. The gene function GO analysis and KEGG pathway enrichment analysis were performed through the DAVID database, and bubble charts were drawn using R-studio software. Use Cytoscape to draw a network diagram of core targets and KEGG pathway. Results A total of 63 active ingredients were obtained in Jisheng Shenqi Pills, and 211 related targets were predicted. A total of 3126 OP related targets were retrieved through the three major databases; 132 targets were compounded with disease. The intersection gene and protein interaction network map and core target-pathway network map were constructed by Cytoscape. The arrangement according to the size of the nodes shows that Jisheng Shenqi Wan mainly acts on target genes such as AKT1, MAPK1, IL6, MAPK8, JUN, VEGFA and regulation Signal pathways such as TNF, IL-17, AGE-RAGE, Fluid shear stress and atherosclerosis play a role in treating OP. Conclusion Jisheng Shenqi Pill has the characteristics of multi-component, multi-target and multi-system in treating OP. Its mechanism of action may be through inhibiting osteoclast formation, stimulating osteoblast activity, regulating bone metabolism balance, reducing inflammatory response, etc. Approach.

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