湿热痹阻型痛风性关节炎中药治疗数据挖掘及作用机制研究

Data Mining and Mechanism Research of Traditional Chinese Medicine Treatment for Gouty Arthritis of Damp-heat Obstruction

[目的]挖掘中医药治疗湿热痹阻型痛风性关节炎的处方用药规律,并分析核心处方药物可能的作用机制。[方法]检索中国知网(China National Knowledge Infrastructure,CNKI)、万方数据知识服务平台(WanFang Database)、维普中文科技期刊数据库(VIP Chinese Scientific Journal Database)、中国生物医学文献数据库(China Biology Medicine disc,CBMdisc)中痛风性关节炎相关的临床文献,构建方药数据库,通过频次统计、关联规则、复杂网络及系统聚类进行处方用药规律分析,通过中药分子机制生物信息学分析工具(Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine,BATMAN-TCM)对核心处方进行疾病及京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。[结果]共纳入文献241篇,483首处方,涉及中药311味,主要为12类,前3位为清热药、利水渗湿药、补虚药,用药频次达7 707次,频次>50的共计36味。药物四气以寒为主,五味以甘、苦为主,归经以脾、胃经为主。关联规则得到常用药物组合18组,二项关联组合20项,三项关联组合26项。系统聚类得到12组药物常用组合。复杂网络分析提示,核心处方为土茯苓、薏苡仁、牛膝、苍术、黄柏、萆薢,以上药物配伍富集的生物学通路有48条,与痛风相关的信号通路有4条。[结论]中医药治疗湿热痹阻型痛风性关节炎紧扣湿热痰浊瘀毒的病机特点,治疗以清热利湿健脾为核心,佐以解毒泄浊除痹、活血通络止痛、祛风湿利关节等法。核心处方用药可能是通过嘌呤代谢通路和神经活性配体受体相互作用信号通路,调节黄嘌呤氧化酶(Xanthine oxidase,XOD)及相关神经递质,发挥降尿酸、止痛作用。

[Objective] To explore the prescription medication rules of traditional Chinese medicine(TCM) in treating gouty arthritis of dampheat obstruction and analyze the possible mechanism of core prescription drugs. [Methods] Through searching China National Knowledge Infrastructure(CNKI), WanFang Data Knowledge Service Platform(Wanfang Database), VIP Chinese Scientific Journal Database(VIP),China Biology Medicine disc(CBMdisc), the database of prescription drugs was constructed, and the regularity of prescription drugs was analyzed by frequency statistics, association rules, complex network and systematic clustering, and the disease and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of core prescriptions were accomplished with Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM). [Results] A total of 241 articles were included, the 483prescriptions involved 311 kinds of Chinese drugs, mainly belonging to 12 categories. The first three were heat-clearing drugs, diuresisinducing and dampness-eliminating drugs, and tonic drugs, with a frequency of 7 707, and there were totaling 36 kinds of Chinese drugs with a frequency of >50. The nature was cold, and flavors were sweet and bitter, and meridian tropism was mainly spleen and stomach meridians. According to the association rules, there were 18 commonly used drug combinations, 20 binomial association combinations and26 triple association combinations. Totally 12 groups of commonly used drug combinations were obtained by systematic clustering. Complex network analysis showed that the core prescription was Rhizoma Smilacis Glabrae, Coicis Semen, Achyranthis Radix, Rhizoma Atracty lodis, Cortex Phellodendri and Rhizoma Dioscoreae Septemlobae, and there were 48 biological pathways of drug compatibility enrichment and 4 signaling pathways related to gout. [Conclusion] Treatment of gouty arthritis due to damp-heat obstruction by TCM is closely related to the pathogenesis of damp-heat phlegm and blood stasis. The core of treatment is to clear away heat, promote diuresis and invigorate the spleen, supplemented by detoxification and turbidity, activate blood circulation, dredge collaterals and relieve pain, expel wind and damp and benefit joints. The core prescription may regulate Xanthine oxidase(XOD) and related neurotransmitters play the role of lowering uric acid and relieving pain through purine metabolism pathway and neural activity ligand receptor interaction signaling pathway.