基于网络药理学研究杜仲治疗骨质疏松性骨折的作用机制
Study on the mechanism of eucommiae in the treatment of osteoporotic fracture based on network pharmacology
  
DOI:10.3969/j.issn.1006-7108.2021.05.020
中文关键词:  中医中药  杜仲  骨质疏松性骨折  网络药理学  作用机制
英文关键词:traditional Chinese medicine  eucommiae  network pharmacology  osteoporotic fracture  mechanism
基金项目:国家自然科学基金项目(81973886,81674004)
作者单位
门志涛1,2 徐敏2 黄承军2 万雷3 马江涛1 黄宏兴1,3* 1.广州中医药大学广东 广州 510006 2.柳州市中医医院广西 柳州 545001 3.广州中医药大学第三附属医院广东 广州 510378 
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中文摘要:
      目的 基于网络药理学研究杜仲治疗骨质疏松性骨折的分子作用机制。方法 利用TCMSP计算系统生物学实验室、GeneCards数据库,分别对杜仲的有效成分、杜仲的治疗靶点和骨质疏松性骨折的靶标进行筛选,然后利用R语言软件对杜仲治疗靶点与骨质疏松性骨折疾病靶标进行取交集,得到中药-疾病靶标,再利用Cytoscape技术对杜仲的多组分、多靶点、多通路、多疾病网络进行可视化研究,构建中药-疾病-成分-靶标的调控网络,然后通过构建杜仲与骨质疏松性骨折靶标的相互作用网络图以及柱状图,从而筛选得到其关键核心的靶标。最后对核心靶标进行GO和KEGG分析。结果 筛选得到杜仲治疗骨质疏松性骨折19个有效成分,59个中药-疾病靶标,杜仲-骨质疏松性骨折靶标涉及的GO功能富集的结果包括核受体的活动、转录因子活性、类固醇激素受体活性等。杜仲-骨质疏松性骨折靶标涉及的KEGG信号通路富集分析的结果主要包括:细胞凋亡信号通路、内分泌抵抗、p53信号通路、MAPK信号通路、NF-kappaB信号通路、PI3K-Akt信号通等。结论 杜仲治疗骨质疏松性骨折的作用机制是杜仲中所含有的多个有效成分调节骨质疏松骨折愈合过程中的多个相关的基因,进而介导了骨折愈合过程中的多条信号通路,经与相关文献报道信息整合发现,杜仲治疗骨质疏松性骨折的调控信号通路主要为细胞凋亡、PI3K-Akt、MAPK、p53、NF-kappaB等信号通路,这些通路通过直接或间接调节骨代谢稳态平衡,最终达到治疗骨质疏松性骨折的目的。
英文摘要:
      Objective To identify the the molecular mechanism of eucommiae in the treatment of osteoporotic fracture based on network pharmacology. Methods The chemical components and targets for the therapeutic actions of eucommiae were screened using the TCMSP database and the GeneCards database. The intersection of therapeutic target of eucommiae and the target of osteoporosis disease was obtained with R software. Cytoscape was used to visualize the multiple components-multiple target-multiple pathways-multiple disease network of eucommiae. The regulatory network of TCM-component-disease-target was constructed. The core target was screened by constructing the protein-protein interaction (PPI) network and bar graph of the TCM-disease target. Pathway enrichment analysis was performed using the GO function enrichment analysis and KEGG pathway enrichment analysis. Results There were 19 active components in the treatment of osteoporotic fracture and 59 traditional Chinese medicine-disease targets. The enrichment of GO function involved in eucommiae-OPF target included nuclear receptor activity, transcription factor activity, steroid receptor activity and so on. The results of enrichment analysis of KEGG signal pathways involved in eucommiae-osteoporotic fracture target mainly included apoptosis signal pathway, endocrine resistance, p53 signal pathway, MAPK signal pathway, NF-kappaB signal pathway, and PI3K-Akt signal pathway. Conclusion The mechanism of eucommie in the treatment of osteoporotic fracture is that multiple active components in eucommie regulate several related genes in the process of osteoporotic fracture healing, and then mediate multiple signal pathways in the process of fracture healing. Through the integration of information reported in related literature, it is found that these pathways mainly include apoptosis, PI3K-Akt, MAPK, p53, NF-kappaB, and so on. These pathways regulate the homeostasis of bone metabolism directly or indirectly, and finally achieve the purpose of treating osteoporotic fractures.
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