基于网络药理学及动物实验研究祛风汤治疗肛周湿疹的作用机制  

Exploring Mechanism of Qufeng Tang(祛风汤)against Perianal Eczema Based on Network Pharmacology and Animal Experiments

作　　者：霍旺[1] 李晗 曹科[1] 叶宇飞[1] 徐慧岩[1] 肖新凯 刘莉[1] 宋玲 高云航 杨依霏[2] HUO Wang;LI Han;CAO Ke;YE Yufei;XU Huiyan;XIAO Xinkai;LIU Li;SONG Ling;GAO Yunhang;YANG Yifei(Department of Traditional Chinese Medicine,The Sixth Medical Center of PLA General Hospital,Beijing 100853,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]解放军总医院第六医学中心中医医学部,北京100853 [2]中国中医科学院中药研究所,北京100700

出　　处：《中医药导报》2024年第11期41-47,共7页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：北京市中医药薪火传承“3+3”工程立项韩宝基层老中医传承工作室(2021-JC-1);北京市中医管理局第六批北京市级中医药专家学术经验继承工作项目(京中医科字〔2021〕169号);第七批全国老中医药专家学术经验继承工作项目(国中医药办人教发〔2021〕17号);中国中医科学院优秀青年科技人才培养专项(ZZ16-YQ-027)。

摘　　要：目的:基于网络药理学方法探究祛风汤治疗肛周湿疹的作用机制,并通过动物实验对关键靶点及信号通路进行验证。方法:应用中药系统药理学数据库与分析平台(TCMSP)数据库获得祛风汤10味中药相关活性成分及作用靶点;通过GeneCards数据库和OMIM数据库筛选肛周湿疹的疾病靶点,并采用Venny 2.1.0在线软件作图工具平台获取两者交集基因;基于String数据库构建祛风汤治疗肛周湿疹交集靶点PPI网络,并通过构建Hub网络筛选核心靶点。应用DAVID6.8数据平台对交集靶点的基因本体论(GO)生物学过程富集分析和京都基因与基因组百科全书(KEGG)通路进行注释分析。通过Cytoscape构建祛风汤“活性成分-靶点-通路”网络筛选主要活性成分。构建肛周湿疹小鼠模型,验证祛风汤治疗肛周湿疹的关键靶点及信号通路。结果:祛风汤共有135个活性成分,对应268个作用靶点,其中35个作用靶点与治疗肛周湿疹有关。PPI网络分析得到白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、CXCL8(IL-8)等核心靶点。GO富集分析共得到267个条目;KEGG富集分析共筛选得到60条通路,主要涉及TNF信号通路、核因子κB(NF-κB)信号通路、类风湿关节炎等。动物实验结果显示,祛风汤可改善肛周湿疹小鼠皮肤损伤,减少局部炎症浸润;祛风汤能减少肛周湿疹小鼠血清IL-6含量(P<0.05),下调湿疹皮肤组织中NF-κB信号通路相关蛋白NF-κB和TNF-α表达水平(P<0.05)。结论:祛风汤治可能通过调控NF-κB信号通路发挥疗治疗肛周湿疹的作用。Objective:To explore the mechanism of Qufeng Tang(QFT)in treatment of perianal eczema through network pharmacology and animal experiments.Methods:The active components and targets related to the 10 herbs of QFT were searched through the TCMSP.Perianal eczema disease targets were retrieved and collected from GeneCards and OMIM databases.The intersection genes were obtained by Venny 2.1.0 platform.The PPI network was constructed and analyzed by String online database.The gene ontology biological process enrichment analysis and KEGG pathway annotation analysis were carried out through David database.The network of"active components-targets-pathways"was constructed by using Cytoscape software and then the main active ingredients and targets of QFT were screened.Finally,the perianal eczema models were constructed in mice to verify the key targets and signaling pathways of QFT in the treatment of perianal eczema.Results:After screening,there are 135 active components and 268 corresponding targets of QFT,and 35 targets were related to the treatment of perianal eczema.The PPI network identified core targets including IL-6,TNF,CXCL8(IL-8),and so on.The GO functional enrichment analysis yielded a total of 267 entries.KEGG enrichment analysis identified 60 pathways,mainly involving the TNF signaling pathway,NF-κB signaling pathway,and rheumatoid arthritis.The results of animal experiments indicated that QFT can improve the skin damage and reduce inflammation infiltration in mice with perianal eczema.QFT significantly reduced the serum level of IL-6(P<0.05),and down-regulated the expression of NF-κB and TNF-α(P<0.05),related proteins in the NF-κB signaling pathway.Conclusion:QFT may have therapeutic effects on perianal eczema by regulating the NF-κB signaling pathway.

关 键 词：肛周湿疹 祛风汤 NF-ΚB信号通路 网络药理学 作用机制 小鼠 

分 类 号：R285.5[医药卫生—中药学]