世界中医药
文章摘要
引用本文:刘剑1,杨雷2,沈浮2,聂颖1.补肾活血法治疗腰椎间盘突出症的用药规律和潜在分子机制预测[J].世界中医药,2022,(13):.  
补肾活血法治疗腰椎间盘突出症的用药规律和潜在分子机制预测
Medication Rule of the Method of Tonifying Kidney and Activating Blood for Lumbar Disc Herniation and the Mechanism:Based on Data Mining and Network Pharmacology
投稿时间:2021-05-17  
DOI:10.3969/j.issn.1673-7202.2022.13.012
中文关键词:  腰椎间盘突出症  补肾活血法  方剂  数据挖掘  网络药理学  用药规律  作用机制  京都基因与基因组百科全书富集分析
English Keywords:Lumbar disc herniation  Kidney-tonifying and blood-activating method  Prescription  Data mining  Network pharmacology  Medication rule  Mechanism  KEGG enrichment analysis
基金项目:国家自然科学基金面上项目(81874476)——Wnt信号通路调控“虚、瘀、毒”病机下膝骨关节炎软骨细胞自噬及加味独活寄生合剂的干预机制研究;湖南省科技创新计划项目(2019JJ80071)——基于红核蛋白质组学探讨益气活血法修复脊髓损伤的分子机制
作者单位
刘剑1,杨雷2,沈浮2,聂颖1 1 湖南中医药大学第一附属医院长沙410007 2 湖南中医药大学长沙410208 
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中文摘要:
      目的:挖掘补肾活血法治疗腰椎间盘突出症(LDH)的处方用药规律,利用网络药理学方法对机制进行预测分析。方法:检索国家知识基础设施数据库(CNKI)相关文献,采用中医传承计算平台软件分析处方药物性味归经、关联规则、聚类分析,挖掘核心药物及类方,中药系统药理学数据库与分析平台(TCMSP)收集核心药物的活性成分及潜在靶标,GeneCards,在线人类孟德尔遗传数据库(OMIM)数据库搜集LDH疾病靶点,利用STRING数据库分析核心药物干预LDH的核心靶蛋白,并进行基因本体(GO)和京都基因和基因组百科全书(KEGG)富集分析。结果:纳入104首处方共计233味中药,挖掘得到12个核心药物及5个核心类方,主要来源于补肾活血汤、身痛逐瘀汤和六味地黄汤,得到槲皮素、木犀草素、山柰酚等178个有效活性成分,涉及干预LDH的交集靶标52个,蛋白质-蛋白质相互作用(PPI)网络模型涉及JUN、AKT1、IL-6、MAPK1、VEGFA、FOS、MAPK14等核心靶蛋白,补肾活血类方、滋阴补肾类方、活血化瘀的特征性靶蛋白分别为多巴胺D3受体、胰岛素、维生素D受体,健脾补肾类方与白细胞介素17A、肿瘤坏死因子关系密切。活血通络类方中核心靶蛋白为C-X-C基序趋化因子配体8、核因子κB亚基1。KEGG富集分析涉及肿瘤坏死因子、白细胞介素-17、促分裂原活化的蛋白激酶、磷脂酰肌醇-3-激酶-蛋白激酶B、缺氧诱导因子-1等炎症相关通路,以及Th17细胞分化、T细胞受体信等免疫相关通路。结论:补肾活血法治疗LDH常与通络、健脾、滋阴之法协同运用,其机制可能与抑制局部炎症反应及调节全身免疫平衡等多靶标、多途径共同作用有关。
English Summary:
      To explore the medication rule for lumbar disc herniation (LDH) and predict the mechanism based on network pharmacology.Methods:Related articles were searched from China National Knowledge Infrastructure (CNKI),followed by the analysis of properties,flavors,and meridian tropisms of related medicinals,association rules analysis,and clustering analysis based on Traditional Chinese Medicine Inheritance Computing System (TCMICS) to screen the core medicinals and prescriptions.The active components and potential targets of core medicinals were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP),and targets of LDH from GeneCards and Online Mendelian Inheritance in Man (OMIM).STRING was employed to analyze the key targets of core medicinals against LDH,followed by Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment.Results:A total of 104 prescriptions were retrieved,involving 233 medicinals,and 12 core medicinals and 5 core prescriptions were screened out.The core medicinals were from the Bushen Huoxue Decoction,Shentong Zhuyu Decoction,and Liuwei Dihuang Decoction.A total of 178 effective active components,including quercetin,luteolin,and kaempferol,and 52 anti-LDH targets were obtained.According to the protein-protein interaction (PPI) network,the core targets were JUN,protein kinase B (AKT1),interleukin-6 (IL6),mitogen-activated protein kinase 1 (MAPK1),vascular endothelial growth factor A (VEGFA),FOS,mitogen-activated protein kinase 14 (MAPK14),etc.The characteristic target proteins of Bushen Huoxue Formulas,Ziyin Bushen Formulas,and Huoxue Huayu Formulas were dopamine receptor D3 (DRD3),insulin (INS),and vitamin D receptor (VDR),respectively.The Jianpi Bushen Formulas were closely related to interleukin 17A (IL17A) and tumor necrosis factor (TNF).The core target proteins of the Huoxue Tongluo Formulas were C-X-C motif chemokine ligand 8 (CXCL8) and nuclear factor kappa B subunit 1 (NFKB1).The key targets were involved in the following KEGG pathways:inflammation-related pathways of TNF,IL-17,MAPK,PI3K-Akt,and hypoxia-inducible factor-1 (HIF-1) pathways,and immune-related pathways such as Th17 cell differentiation and T cell receptor pathways.Conclusion:The treatment of LDH by kidney-tonifying and blood-activating method is often coordinated with dredging collaterals,invigorating spleen,and tonifying yin.The mechanism is the likelihood that it inhibits local inflammatory response and regulates systemic immune balance with multiple targets and multiple pathwways.
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