痛风相关国家发明专利中药组方的用药规律及机制探讨  

Analyze the Laws and Mechanism of the National Patent Chinese Herbal Prescription for Gout

作　　者：高旖旎 张祎 张凤琦 张莉[2] 孙静 谢志军[1] GAO Yini;ZHANG Yi;ZHANG Fengqi(Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]浙江中医药大学,杭州310053 [2]浙江中医药大学附属杭州市中医院 [3]浙江中医药大学附属第二医院

出　　处：《浙江中医药大学学报》2024年第1期113-121,130,共10页Journal of Zhejiang Chinese Medical University

基　　金：浙江省教育厅科研项目(Y202146162);浙江省自然科学基金项目(Y21H270014);浙江省中医药科技计划项目(2020ZZ006);国家重点研发计划项目(2022YFC3501204)。

摘　　要：[目的]探讨痛风相关国家专利中药组方的用药规律,并分析核心药物的作用机制。[方法]通过中国专利公布公告网站检索治疗痛风的中药组方,提取数据并构建数据库。通过频数统计、Apriori算法、因子分析及系统聚类方法进行用药特点分析。在中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)中获取核心药物组合的中药靶点,在人类基因数据库(Human Gene database,GeneCards)、人类在线孟德尔遗传(Online Mendelian Inheritance in Man,OMIM)数据库中获得痛风疾病靶点,取两者靶点交集,将其导入Cytoscape 3.9.1软件,应用ClueGo插件对药物组合进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。将交集靶点导入STRING数据库,构建蛋白互作(protein-protein interaction,PPI)网络,选取部分关键靶点,使之与对应的中药活性化合物进行分子对接。[结果]纳入治疗痛风的专利中药组方共508项,涉及中药401味,用药频数共6082次,药物类别以利水渗湿药为主,其次为补虚药、清热药及活血化瘀药等。关联规则分析得到二项关联规则3条,三项关联规则5条。因子分析共提取出8个公因子。系统聚类分析得到3组药物组合,药物组合富集的共同生物学通路56条。分子对接结果显示,槲皮素与肿瘤坏死因子(tumor necrosis factor,TNF)的结合效果最好,黄芩素与白介素-6(interleukin-6,IL-6)结合效果次之,槲皮素与三磷酸腺苷结合盒转运蛋白2(adenosine triphosphate binding cassette super family G member 2,ABCG2)的结合效果较好。[结论]治疗痛风的国家专利组方多以“湿浊瘀阻”为核心病机,从湿、瘀、虚三方面治疗痛风,药物组合常以四妙散、茯苓泽泻汤和四物汤为基础加减,其主要通过TNF、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)、Toll样受体(Toll-like receptors,TLRs)、IL-17等信号�[Objective]To explore the medication rule of TCM compound patent in the treatment of gout,and analyze the mechanism of action of the core herbs based on the national patent database.[Methods]The Chinese herbal compound patent database for gout treatment was retrieved and entered into the Website of China Patent Announcement of The State Intellectual Property Office.The characteristics of medications were analyzed by frequency statistics,Apriori algorithm,factor analysis and systematic clustering method.The Chinese herbs targets of the core herbs combinations were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the gout disease targets were obtained from Human Gene database(GeneCards)and Online Mendelian Inheritance in Man(OMIM)database.The intersection of the two targets was imported into Cytoscape 3.9.1 software,and the Cluego plug-in was used to complete the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the herb combinations.The intersection targets were imported into STRING database to obtain protein-protein interaction(PPI)network,and some key targets were selected for molecular docking with corresponding active compounds of Chinese herbs.[Results]A total of 508 Chinese herbal compound patents were included in the treatment of gout,involving 401 Chinese herbs,and the frequency of herbs was 6082 times.Chinese herbs for diuresisinducing and dampness-draining were mainly used,followed by herbs for tonifying deficiency,clearing heat,promoting blood circulation and removing blood stasis.The analysis of association rules obtained 3 binomial association rules and 5 trinomial association rules.Eight common factors were extracted by factor analysis.Three groups of herbs combinations were obtained by systematic clustering analysis,and 56 common biological pathways of herbs combination enrichment were found.Molecular docking results showed that the combination of Quercetin and tumor necrosis factor(TNF)was the best,followed by Bai

关 键 词：痛风 专利 数据挖掘 中药 用药规律 机制 

分 类 号：R658[医药卫生—外科学]