蒲辅周治疗乙脑的用药规律及机制探讨OA
Based on Data Mining and Network Pharmacology,this Study Explores the Medication Patterns and Mechanisms of Pu Fuzhou in the Treatment of Japanese Encephalitis
目的:通过数据挖掘技术和网络药理学技术探讨蒲辅周治疗流行性乙型脑炎(乙脑)的中药用药规律及机制.方法:人工检索《蒲辅周医疗经验》《中国百年百名中医临床家丛书—蒲辅周》《蒲辅周医学真传——外感热病传承心悟》等相关治疗乙脑的医案,纳入符合条件的中药治疗乙脑的相关文献.利用 Excel 软件统计中药性味归经;通过 R 4.2.1 语言平台,采用 Apriori 算法(支持度阈值≥0.15,置信度≥0.75)对高频药物(TOP20)进行关联规则挖掘,并实施层次聚类分析(欧氏距离法)提取核心药组.选用聚类分析得到的核心方,基于 TCMSP v2.3 数据库(OB≥30%,DL≥0.18)获取核心组方化合物数据集,通过 UniPort 数据库进行靶点校正,在 GeneCards 数据库、人类孟德尔遗传数据库(OMIM)检索与乙脑相关的疾病基因,然后进行交集分析获得共同基因,采用 Cytoscape 3.10.0构建核心靶点蛋白质-蛋白质相互作用(PPI)网络(STRING置信度≥0.7),结合CytoHubba插件识别关键靶点(MCC算法 TOP10).运用 Metascape 平台(P<0.01)进行 GO/KEGG 多层次注释,构建中药-成分-靶点-通路多维网络模型.结果:共纳入方剂 30 首,包含 167 味中药,使用频次排名前 20 的中药有生甘草(36 次)、连翘(25 次)、厚朴(25次)、滑石(25 次)、大黄(22 次)等.药性主要以寒性、温性和平性为主,药味主要以甘味、辛味和苦味为主,主要研究中药归于肺、脾和胃三经.关联规则分析得到朱砂-麝香等药物组合.聚类分析形成 3 个新的药物组合,第 1 类药物组合(朱砂、麝香、犀角、黄连、黄芩、栀子、大黄、芒硝)可能为中药治疗 TI 的核心方.槲皮素、山奈酚、芹菜素等是核心方治疗 TI 的关键成分,这些成分可能作用于 RAC-α 丝氨酸/氨酸-蛋白激酶(TNF)、白介素-6(IL6)、蛋白激酶 B(AKT1)、白介素-1B(IL1B)、前列腺素 G/H 合成酶 2(PTGS2)、肿瘤蛋白 P53(TP53)、原癌基因(JUN)等靶点,并通过癌症核心通路、AGE-RAGE 介导的糖代谢紊乱、脂质异常相关病理(动脉粥样硬化)等信号通路发挥作用.结论:临床治疗乙脑多用辛凉透邪、清热解毒、开窍豁痰类中药,核心方可能通过癌症核心通路、AGE-RAGE 介导的糖代谢紊乱、脂质异常相关病理(动脉粥样硬化)等信号通路参与调节氧化应激及炎症反应等过程,发挥对乙脑的治疗作用.
Objective:To explore the patterns and mechanisms of traditional Chinese medicine(TCM)use in treating Japanese encephalitis(JE)by PU Fuzhou using data mining and network pharmacology techniques.Methods:Relevant medical records on JE treatment were manually retrieved from publications such as"Pu Fuzhou's Medical Experi-ence,""One Hundred Famous TCM Clinicians in China's Century-Old Series—PU Fuzhou,"and"Pu Fuzhou's True Medical Transmission—Insights into the Inheritance of Exogenous Febrile Diseases."Literature on TCM treatment of JE that met the criteria was included.The properties,flavors,and meridian tropism of TCM herbs were statistically analyzed using Excel software.Using the R 4.2.1 platform,the Apriori algorithm(support threshold≥0.15,confidence≥0.75)was employed to mine association rules for the top 20 high-frequency drugs,and hierarchical cluster analysis(Euclidean distance method)was implemented to extract the core drug groups.The core formula obtained from cluster analysis was selected.A dataset of core formula compounds was obtained from the TCMSP v2.3 database(OB≥30%,DL≥0.18).Target correction was performed using the UniPort database.Disease genes related to Japanese encepha-litis were retrieved from the GeneCards database and the Human Mendelian Inheritance Database(OMIM).Intersection analysis was then performed to obtain common genes.A protein-protein interaction(PPI)network for the core target was constructed using Cytoscape 3.10.0(STRING confidence≥0.7).Key targets were identified using the CytoHubba plugin(MCC algorithm TOP10).GO/KEGG multi-level annotation was performed using the Metascape platform(P<0.01),constructing a multi-dimensional network model of traditional Chinese medicine,components,targets,and pathways.Results:A total of 30 prescriptions containing 167 Chinese medicinal herbs were included.The top 20 most frequently used herbs included licorice root(36 times),forsythia(25 times),magnolia bark(25 times),talc(25 times),and rhubarb(22 times).The properties of the herbs were mainly cold,warm,and neutral,and the flavors were mainly sweet,pun-gent,and bitter.The main focus of the study was on the lung,spleen,and stomach meridians.Association rule analysis revealed combinations such as cinnabar and musk.Cluster analysis identified three new drug combinations.The first combination(cinnabar,musk,rhinoceros horn,coptis,scutellaria,gardenia,rhubarb,and mirabilite)may be the core prescription for treating TI with Chinese medicine.Quercetin,kaempferol,and apigenin are key components of the core formula for treating Japanese encephalitis(TI).These components may act on targets such as RAC-α serine/amino acid-protein kinase(TNF),interleukin-6(IL6),protein kinase B(AKT1),interleukin-1B(IL1B),prostaglandin G/H synthase 2(PTGS2),tumor protein P53(TP53),and proto-oncogenes(JUN),and exert their effects through signaling pathways such as the cancer core pathway,AGE-RAGE-mediated glucose metabolism disorders,and lipid abnormal-ity-related pathology(atherosclerosis).Conclusion:Clinical treatment of Japanese encephalitis often uses traditional Chinese medicine with pungent and cooling properties to dispel pathogens,clear heat and detoxify,and open the orific-es to resolve phlegm.The core formula may exert its therapeutic effect on Japanese encephalitis by participating in the regulation of oxidative stress and inflammatory responses through signaling pathways such as the cancer core pathway,AGE-RAGE-mediated glucose metabolism disorders,and lipid abnormality-related pathology(atherosclerosis).
董宇昂;林峙豪;叶海鹏;张冬阳;曹宇翔;张珺
安徽中医药大学第一临床医学院 安徽 合肥 230012安徽中医药大学第一临床医学院 安徽 合肥 230012安徽中医药大学第一临床医学院 安徽 合肥 230012安徽中医药大学第一临床医学院 安徽 合肥 230012安徽中医药大学第一临床医学院 安徽 合肥 230012安徽中医药大学中医学院 安徽 合肥 230012
医药卫生
蒲辅周乙脑数据挖掘网络药理学
PU FuzhouJapanese encephalitisData miningNetwork pharmacology
《中医药临床杂志》 2026 (5)
977-986,10
国家自然科学基金委员会,面上项目(82174160)安徽省高等学校科学研究项目(2023AH050752)安徽省高等学校科学研究项目(2024AH051038)
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