基于网络药理学及分子对接探讨透脓散以IL-6为核心的免疫炎症调控干预肉芽肿性乳腺炎的机制及验证研究  

IL-6 Centered Immune-Inflammatory Regulation Mechanism of Tounong San in Intervening GLM Based on Network Pharmacology and Molecular Docking

作　　者：刘春妘 刘晓菲[1,2,3] 孙颖 陈翰翰 张丽美[4] LIU Chunyun;LIU Xiaofei;SUN Ying;CHEN Hanhan;ZHANG Limei(Shandong University of Traditional Chinese Medicine,Jinan 250014,China;Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,China;Shandong Province Collaborative Innovation Center of Traditional Chinese Medicine Classics,Jinan 250014,China;Shandong Academy of Chinese Medicine,Jinan 250014,China)

机构地区：[1]山东中医药大学,山东济南250014 [2]山东中医药大学附属医院,山东济南250014 [3]山东省中医经典名方协同创新中心,山东济南250014 [4]山东省中医药研究院,山东济南250014

出　　处：《中医药信息》2023年第1期43-51,共9页Information on Traditional Chinese Medicine

基　　金：山东省自然科学基金面上项目(ZR2020MH356);山东省医药科技发展计划项目(2018WS191);国家重点研发项目“中医药现代化研究”(2018YFC1704103);山东省重点研发计划项目(2015GSF119014);山东省中医药科技发展计划项目(2019-0159);山东省卫生健康委员会、山东省中医药管理局资助项目。

摘　　要：目的:应用网络药理学及分子对接技术探讨透脓散治疗肉芽肿性乳腺炎(GLM)的作用机制,并通过临床研究初步验证透脓散干预的以IL-6为核心的免疫炎症调控机制。方法:利用中药系统药理学数据库分析平台(TCMSP)搜集透脓散药物活性成分,GeneCards、OMIM、TTD数据库查询GLM的疾病相关靶点基因,韦恩在线系统构建透脓散-肉芽肿性乳腺炎的交集靶点,Cytoscape软件构建“药物-成分-靶点”网络图,将交集基因导入构建蛋白互作网络及拓扑分析,Metascape平台进行GO、KEGG富集分析,OmicShare在线平台构建气泡图并构建靶点通路网络图,分子对接软件(Autoduck)将核心靶点与核心活性成分进行分子对接,Pymol软件将分子对接结果可视化。临床研究选择80例GLM患者随机分为治疗组和对照组。治疗组口服透脓散,对照组采用激素治疗,两组均治疗20 d。分别于治疗前后采用空心针穿刺原肿块组织,包埋组织为病理蜡块、切片并进行免疫组化法染色、中性树胶封片,显微镜下观察进行验证。结果:透脓散治疗GLM的靶点基因共969个,GLM相关靶点79个,交集靶点18个。拓扑分析相关靶点126个,主要涉及核心靶点IL-6、TNF、IFN-γ和IL-1β等;GO生物过程主要涉及炎症反应、免疫反应、MAPK级联等;KEGG信号通路主要涉及NF-κB信号通路、Jak-STAT信号通路、TNF信号通路等;分子对接显示核心靶点IL-6、TNF、IL-1β与核心活性成分结合能良好。临床研究结果则显示透脓散可明显降低IL-6、TNF、IL-1β的阳性表达。结论:透脓散能通过多成分、多靶点、多通路调控GLM免疫炎症反应,临床研究进一步验证了其对肉芽肿乳腺炎的治疗疗效及以IL-6为核心的免疫炎症调控机制,为透脓散治疗GLM的作用机制提供了理论支持。Objective: To explore the action mechanism of Tounong San in treating granulomatous mastitis(GLM) through applying network pharmacology and molecular docking technology, and to conduct preliminary verification of the IL-6 centered immune-inflammatory regulation mechanism of Tounong San through clinical trials. Methods: The TCM System Pharmacology Database Analysis Platform(TCMSP) was used to collect the active ingredients of Tounong San, the corresponding disease-related target genes of GLM were searched from the databases of GeneCards, OMIM and TTD. Venn online system was applied to obtain the intersection target of Tounong San-GLM, Cytoscape software was used to construct a ’drugcomponent-target’ network diagram, and introduce the intersection gene for protein interaction network and topology analysis. The Metascape platform was applied to conduct GO analysis and KEGG enrichment analysis, and OmicShare online platform was applied to construct a bubble chart and a target pathway network diagram. Molecular docking software(Autoduck) was used to dock the core target with the core active ingredients. The results of molecular docking were visualized through molecular drawing software(Pymol).80 cases of GLM were selected and randomly divided into the treatment group and the control group for the clinical study. The treatment group was treated with Tounong San, and the control group was treated with hormone. Both groups were treated for 20 days. The original tumor tissue was punctured with a hollow needle, and the embedded tissue was used as pathological wax block, sectioned, and stained by HE method and immunohistochemical method. Neutral gum was sealed for microscope observation. Results: Tounong San treated 969 GLM target genes, 79 GLM-related targets, and 18 intersection targets. 126 targets were obtained through topology analysis, which mainly involved IL-6, TNF, IFN-γ and IL-1β. GO biological process mainly involved inflammation, immune response and MAPK cascade. KEGG signaling pathway mainly involved NF-�

关 键 词：透脓散 肉芽肿性乳腺炎 网络药理学 分子对接 实验验证 IL-6 

分 类 号：R285[医药卫生—中药学]