基于网络药理学及实验验证探讨敦煌医方小补肝汤抗运动性疲劳的作用机制  

Mechanism of Dunhuang(敦煌)Medical Prescription Xiaobugan Decoction(小补肝汤)against Exercise-Induced Fatigue Based on Network Pharmacology and Experimental Validation

作　　者：芦文娟 张禄璐 梁永林 霍敏峰[1] 张李香 LU Wenjuan;ZHANG Lulu;LIANG Yonglin;HUO Minfeng;ZHANG Lixiang(School of Basic Medicine,Gansu University of Chinese Medicine,Lanzhou 730030;Key Laboratory of Dunhuang Medicine,Ministry of Education,Lanzhou 730030)

机构地区：[1]甘肃中医药大学基础医学院,兰州730030 [2]敦煌医学与转化教育部重点实验室,兰州730030

出　　处：《中药药理与临床》2024年第6期25-32,共8页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家社会科学基金(编号:18XMZ031)。

摘　　要：目的:运用网络药理学及实验验证的方法探讨小补肝汤干预运动性疲劳的有效成分及可能作用机制。方法:在中药系统药理学分析平台(TCMSP)检索小补肝汤的活性成分;通过人类基因组数据库(Genecards)、药物数据库(Drugbank)、在线人类孟德尔遗传(OMIM)、遗传药理学与药物基因组学数据库(PharmGkb),获取疾病的靶标基因;利用Venny2.1.0在线工具绘制药物与疾病靶点的韦恩图,获得交集靶点,将其导入STRING数据库,构建蛋白相互作用(PPI)网络图,通过Bioconductor等在线软件进行基因组数据的高通量分析,得到基因本体(GO)生物功能注释图和京都基因与基因组百科全书(KEGG)富集通路图,预测作用通路,并采用动物实验验证网络药理学预测结果。结果:通过筛选得到小补肝汤36种活性成分,药物-疾病共同靶点244个;通过构建药物-成分-靶点-疾病调控网络,筛选出豆甾醇(Stigmasterol)、海风藤酮(Kadsurenone)、β-谷固醇(Beta-sitosterol)、山蒟酮C(Hancinone C)及黄杉素(Taxifolin)等核心成分;通过蛋白互作网络的构建,筛选出AKT1、GNAQ及PTGS2等11个关键靶点;GO富集分析得出生物学过程BP 3675个,包括对药物的反应、对氧含量的反应、对缺氧的反应等;细胞组分379个,包括膜筏、膜微区、线粒体外膜等;分子功能624个,包括DNA-结合转录因子结合、泛素蛋白连接酶结合及G蛋白偶联胺受体活性等;KEGG富集分析得出涉及的信号通路主要有钙信号通路(GNAQ-PLCB2-IP3R1-CAM)、cAMP信号通路和甲状腺激素信号等通路。动物实验结果显示,与正常对照组比较,模型对照组负重游泳力竭时间显著减少,血清中乳酸(LD)、尿素氮(BUN)的含量显著升高,肝糖原与肌糖原的含量显著降低(P<0.01),骨骼肌组织病理可见骨骼肌细胞排列紊乱不均,有较多炎症细胞弥漫浸润,骨骼肌组织GNAQ、PLCB2、IP3RI、CAM蛋白表达显著上调(P<0.01);与模型对照组比较,各�Objective:To investigate the effective components and possible mechanisms of Xiaobugan Decoction(小补肝汤)against exercise-induced fatigue by network pharmacology and experimental validation.Methods:The active components of Xiaobugan Decoction were searched in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The disease-related target genes were retrieved from Genecards,Drugbank,Online Mendelian Inheritance in Humans(OMIM),and Pharmacogenetics and Pharmacogenomics Knowledge Base(PharmGkb).Venny2.1.0 was used to draw the Wayne diagram of the drug and disease targets,to obtain the intersection targets,which were imported into STRING for construction of the protein-protein interaction(PPI)network.High-throughput genomic sequencing was performed through Bioconductor and other online software,and the gene ontology(GO)annotation map and Kyoto gene and genome Encyclopedia(KEGG)enrichment pathway maps were obtained to predict the pathways involved.Animal experiments were carried out to validate the predictions of network pharmacology.Results:A total of 36 active components were screened,and 244 intersection targets were obtained.By the drug-component-target-disease network constructed,core components such as stigmasterol,kadsurenone,beta-sitosterol,hancinone C and taxifolin were screened.Eleven key targets,including AKT1,GNAQ,and PTGS2,were screened through PPI network.GO enrichment analysis yielded 3675 biological processes(including responses to drugs,oxygen content,and hypoxia),379 cellular components(including membrane rafts,membrane microregions,and mitochondrial outer membrane),and 624 molecular functions(including DNA-transcription factor binding,ubiquitin-protein ligase binding,and G-protein-coupled amine receptor activity).KEGG enrichment analysis found that the main signaling pathways involved were calcium signaling pathway(GNAQ-PLCB2-IP3R1-CAM),cAMP signaling pathway,thyroid hormone signaling pathways,etc.The animal experiments showed,compared with the conditions in n

关 键 词：小补肝汤 网络药理学 运动性疲劳 鸟嘌呤核苷酸结合蛋白q肽 钙离子 

分 类 号：R285[医药卫生—中药学]