补骨脂-淫羊藿对类风湿关节炎抗炎机制的分子对接分析:动物实验验证  

Molecular docking analysis of the anti-inflammatory mechanism of Cibotium barometz and Epimedium for rheumatoid arthritis:animal experiment validation

作　　者：冉磊 韩海慧 徐博 王建业 沈军 肖涟波 施杞[3] Ran Lei;Han Haihui;Xu Bo;Wang Jianye;Shen Jun;Xiao Lianbo;Shi Qi(Shanghai Guanghua School of Clinical Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Joint Surgery,Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200052,China;Institute of Integrated Traditional Chinese and Western Medicine for Arthritis,Shanghai Institute of Traditional Chinese Medicine,Shanghai 200052,China)

机构地区：[1]上海中医药大学光华临床医学院,上海市201203 [2]上海中医药大学附属光华医院关节外科,上海市200052 [3]上海市中医药研究院中西医结合关节炎研究所,上海市200052

出　　处：《中国组织工程研究》2024年第2期208-215,共8页Chinese Journal of Tissue Engineering Research

基　　金：上海市卫生健康委员会上海市临床重点专科建设项目(shslczdzk04801),项目负责人:肖涟波;上海市自然基金面上项目(22ZR1453100),项目负责人:肖涟波;上海市中医临床高地重点领域建设[ZY(2021-2023)-0201-06],项目负责人:肖涟波;上海市自然基金面上项目(22ZR1453000),项目负责人:沈军。

摘　　要：背景:临床上补骨脂-淫羊藿治疗类风湿关节炎疗效明显,但两者所含有效成分复杂,在分子水平上治疗类风湿关节炎的作用机制仍不明确。目的:基于网络药理学和分子对接技术建立胶原诱导型关节炎模型,验证补骨脂-淫羊藿治疗类风湿关节炎可能的作用靶点及通路,为以补骨脂-淫羊藿为主的临床方剂使用提供可靠的实验依据。方法:借助中医药研究平台、中医百科全书和上海有机所的中药与化学成分数据库等检索并筛选有效成分,从PubChem平台获取3D分子式,通过PharmMapper和SwissTargetPrediction平台进行靶标预测;结合DrugBank、GeneCards、OMIM等基因数据库完成类风湿关节炎的疾病靶点获取,经Uniport数据库校准靶标,借助VENNY 2.1获取补骨脂-淫羊藿与疾病交集靶点并绘制韦恩图;采用STRING平台构建蛋白质互作网络图;使用Metascape平台进行基因本体论功能分析及京都基因与基因组百科全书分析,进行数据可视化,利用Cytoscape 3.9.0构建中药-成分-靶点-疾病-通路四重网络模型;运用AutoDock-Vina软件将主要有效成分与核心靶点进行分子对接验证,探索最佳结合靶点。建立Ⅱ型胶原+佐剂诱导型关节大鼠模型,用补骨脂-淫羊藿干预21 d后,观察其对相关通路靶点及炎性细胞因子的影响。结果与结论:①筛选补骨脂与淫羊藿活性成分28个,与类风湿关节炎交集靶点共288个,主要成分有异补骨脂素、补骨脂定、淫羊藿苷等;交集靶点主要有丝氨酸/苏氨酸蛋白激酶1(AKT1)、肿瘤坏死因子、血管内皮生长因子A等;②基因本体论分析获得生物过程2232条,主要与丝氨酸蛋白磷酸化、AKT正调控、活性氧代谢过程等功能有关;③京都基因与基因组百科全书富集分析结果202条,主要有PI3K/AKT信号通路和表皮生长因子受体信号通路等,可能通过调节滑膜细胞凋亡与增殖、抑制炎性因子等发挥治疗作用;④分子对接BACKGROUND:In clinical practice,Cibotium barometz and Epimedium have shown significant efficacy in the treatment of rheumatoid arthritis,but the complex active ingredients contained in the two have an unclear mechanism of action at the molecular level for the treatment of rheumatoid arthritis.OBJECTIVE:Based on network pharmacology and molecular docking technology,to establish a collagen-induced arthritis model and to verify the potential targets and pathways of Cibotium barometz and Epimedium in the treatment of rheumatoid arthritis,providing reliable experimental evidence for the use of clinical formulas with Cibotium barometz and Epimedium as the main components.METHODS:Utilizing traditional Chinese medicine research platforms,traditional Chinese medicine encyclopedias,and databases of traditional Chinese medicine and chemical components from the Shanghai Institute of Organic,effective ingredients were retrieved and identified.3D molecular formulas were obtained from the PubChem platform and target predictions were made using PharmMapper and SwissTargetPrediction.Disease targets for rheumatoid arthritis were obtained from gene databases such as DrugBank,GeneCards,and OMIM.The intersections of targets and Cibotium barometz and Epimedium were plotted using VENNY 2.1 after calibration with the Uniport database.A protein-protein interaction network graph was constructed using the STRING platform.Gene Ontology function analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed using the Metascape platform for data visualization.A four-layered network model of traditional Chinese medicine,ingredients,targets,diseases,and pathways was constructed using Cytoscape 3.9.0.The main effective ingredients were docked with core targets using AutoDock-Vina software to explore the best binding targets.A type II collagen+adjuvant-induced arthritis rat model was established,and the effects of Cibotium barometz and Epimedium on relevant pathway targets and inflammatory cell factors were observed after

关 键 词：网络药理学 分子对接 补骨脂 淫羊藿 类风湿关节炎 凋亡 增殖 体内实验 胶原诱导型关节炎 动物模型 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R593.22