摘要
目的通过网络药理学方法,探讨真武汤治疗类风湿关节炎(RA)的作用机制。方法利用中药系统药理学数据库与分析平台,筛选出真武汤中5味中药的有效成分及其靶点,利用UniProt数据库获取靶点对应的基因。通过Cytoscape软件构建有效化学成分-药物靶点基因网络。在GeneCards数据库中检索RA相关的疾病靶点基因。对药物靶点基因和疾病靶点基因取交集,构建Venn图,将其导入Cytoscape软件构建蛋白-蛋白互作(PPI)网络,并筛选出核心网络。对获得的交集靶点基因进行基因本体(GO)富集分析及京都基因与基因组百科全书(KEGG)通路富集分析,并获得KEGG关系网络。结果共获得有效化学成分23个,对应靶点基因85个,疾病靶点基因1089个,交集靶点基因43个。其中Degree值排名较前的靶点基因为热休克蛋白(HSP)90AA1、雌激素受体1、血管细胞黏附分子1(VCAM1)、雄性激素受体、转录因子P65等。交集靶点基因富集于对脂多糖的反应、对细菌来源分子的反应、对营养水平的反应、对抗生素的反应等841个生物过程,以及流体剪切应力和动脉粥样硬化、糖尿病并发症中的晚期糖基化终产物(AGE)-AGE受体(RAGE)、肿瘤坏死因子(TNF)、白细胞介素(IL)-17等107条信号通路中。结论真武汤可能是通过调节HSP 90AA1、雌激素受体1、VCAM1、雄性激素受体、转录因子P65等靶点,调控流体剪切应力和动脉粥样硬化、糖尿病并发症中的AGE-RAGE、TNF、IL-17等信号通路,来保护内皮细胞、抑制炎症反应及调节免疫能力,从而发挥治疗RA的作用。
Objective To explore the action mechanism of Zhen Wu Tang in the treatment of rheumatoid arthritis(RA)by network pharmacology.Methods The effective components of five Chinese medicines in Zhen Wu Tang and their targets were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the genes corresponding to the targets were obtained using UniProt database.The effective chemical component-target drug gene network was constructed by Cytoscape software.The target disease genes related to RA were retrieved in GeneCards database.Intersection between target drug genes and target disease genes was conducted and a Venn diagram was developed,then protein-protein interaction(PPI)network was constructed by importing the gene intersection to Cytoscape software,and the core network was screened.Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the target genes harvested from the intersection,and the KEGG relational network was obtained.Results In total,23 effective chemical components,85 corresponding target genes,and 1089 target disease genes were retrieved,and 43 target genes were obtained from the intersection.The target genes with leading Degree values included heat shock protein(HSP)90AA1,estrogen receptor 1,vascular cell adhesion molecule 1(VCAM1),androgen receptor,and transcription factor P65.The target genes of intersection were enriched in 841 biological processes and 107 signaling pathways,mainly involved in the biological processes such as response to lipopolysacchride,response to molecule of bacterial origin,response to nutrient levels,response to antibiotics,as well as the signaling pathways such as fluid shear stress and atherosclerosis,advanced glycation end product(AGE)-receptor of AGE(RAGE)in diabetic complications,tumor necrosis factor(TNF),and interleukin(IL)-17.Conclusion Zhen Wu Tang may regulate the targets(HSP90AA1,estrogen receptor 1,VCAM1,androgen receptor,transcription facto
作者
熊海风
刘若雅
李任城
杨博
黎启航
占华松
杨渊
XIONG Hai-feng;LIU Ruo-ya;LI Ren-cheng;YANG Bo;LI Qi-hang;ZHAN Hua-song;YANG Yuan(Graduate School,Guangxi University of Chinese Medicine,Nanning 530001,China;Department of Orthopedics,Guangxi Medical University Kaiyuan Langdong Hospital,Nanning 530021,China)
出处
《广西医学》
CAS
2021年第14期1730-1736,共7页
Guangxi Medical Journal
基金
广西科学研究与技术开发计划(桂科攻1598012-6)
广西中医药大学校级一般硕士研究生科研创新项目(YCSY2020058)。
关键词
类风湿关节炎
真武汤
靶点
信号通路
网络药理学
Rheumatoid arthritis
Zhen Wu Tang
Target
Signaling pathway
Network pharmacology