二仙汤防治骨质疏松症的网络药理学研究
Study on network pharmacology of Erxian decoction in the prevention and treatment of osteoporosis
  
DOI:10.3969/j.issn.1006.7108.2020.04.021
中文关键词:  网络药理学  二仙汤  骨质疏松症  TNF信号通路  HIF-1信号通路
英文关键词:network pharmacology  erxian decoction  osteoporosis  TNF signal pathway  HIF-1 signal pathway
基金项目:山东省中医药科技发展计划项目(2019-0802)
作者单位
王明亮1,2 闫小龙3 田思胜1* 1. 山东中医药大学山东 济南 250355 2. 日照市中医医院山东 日照 276800 3. 山东中医药大学附属医院山东 济南 250014 
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中文摘要:
      目的 通过网络药理学分析二仙汤防治骨质疏松症(osteoporosis,OP)的关键靶点,探讨二仙汤防治OP的可能机制及信号通路。方法 检索中药系统药理学数据库与分析平台(TCMSP),筛选二仙汤的入血活性成分并预测其作用靶点;利用基因表达数据库(GEO)获取GSE56116基因芯片原始数据,分析二仙汤的治疗靶点;从疾病相关数据库检索已知OP致病基因;通过STRING和Cytoscape软件映射获得二仙汤治疗OP的关键靶点,建立关键靶点的蛋白质-蛋白质相互作用(PPI)网络,并进行KEGG和GO富集分析揭示其可能的作用机制。结果 通过检索TCMSP获得符合筛选标准的二仙汤活性成分84个,21个活性成分预测出145个作用靶点;通过R语言对基因芯片进行分析筛选出84个可能致病靶点,通过疾病相关数据平台获得691个OP相关致病靶点,利用STRING和Cytoscape 构建PPI网络筛选出40个关键作用靶点和9个核心作用靶点。KEGG和GO分析结果显示,二仙汤治疗OP的关键靶点主要富集在RNA聚合酶II启动子对转录的正向调节、一氧化氮合酶等生物学进程,主要富集的信号通路为TNF信号通路、低氧诱导因子1信号通路和雌激素信号通路等。结论 通过网络药理学方法阐释二仙汤可能通过TNF信号通路和HIF-1信号通路治疗OP,本研究为揭开中药复方治疗疾病的作用机制提供了科学的方法。
英文摘要:
      Objective To study the potential mechanism and signal pathway of Erxian Decoction in preventing and treating osteoporosis using the method of network pharmacology. Method TCMSP, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, was used to screen the active components in blood of Erxian decoction and to predict the target of active components. The gene chip of GSE56116 was obtained from the expression database (GEO) to predict the target genes related to Erxian decoction, meanwhile, the known genes related to OP were retrieved from six public databases of disease-related gene. The key targets of Erxian decoction in the treatment of OP were obtained by STRING and Cytoscape software mapping, and the protein-protein interaction (PPI) network of key targets was established. KEGG and GO enrichment analysis of the key targets were used to reveal the mechanism of Erxian decoction treating OP. Results 84 active components of Erxian decoction were obtained by searching TCMSP, and 145 targets were predicted by 21 active components. 84 possible pathogenic targets were analyzed and screened by R language. 691 OP related targets were obtained through the public database platform of disease-related genes. STRING and Cytoscape were used to construct PPI networks and 40 key targets and 9 core targets were selected. The results of KEGG and GO analysis showed that the key targets of Erxian decoction in the treatment of OP were mainly enriched in the positive regulation of transcription by RNA polymerase II promoter and the biological processes such as nitric oxide synthase. The main enriched signal pathways were TNF signal pathway, hypoxia inducible factor 1 signal pathway and estrogen signaling pathway. Conclusion Through the method of network pharmacology, it is explained that Erxian decoction may treat OP, through TNF signal pathway and HIF-1 signal pathway. This study provides a scientific method for uncovering the mechanism of traditional Chinese medicine compound in the treatment of diseases.
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