基于数据挖掘探索“以毒攻毒”治疗癥瘕积聚的用药规律

Data Mining of Medication Rules for Treatment of Abdominal Mass with Therapy of“Treating Poison with Poison”

目的从文献角度出发,“以毒攻毒”为科学假说,探索毒性药物治疗癥瘕积聚的用药规律。方法整理《中医方剂大辞典》中收载的治疗癥瘕积聚的方剂,建立方剂数据库,统计分析对癥瘕积聚有治疗作用的总体药物和毒性药物频次、单首方中毒性药物频次、毒性药物功效、药性、药味、归经分布以及中药特征的多因素分析;以Apriori关联规则进行建模分析,Cytoscape 3.9.1软件构建中药核心复杂网络,IBM SPSS Statistics26对核心网络中的药物进行系统聚类分析。结果对筛选出的607首方剂、485味中药进行分析:含毒性药物方剂460首,占比75.78%;使用频次≥50次的高频药物34味,毒性药物11味,占比32.35%;约4/5的方剂中含有毒性药物,约1/5单方组成含≥50%的毒性药物。毒性药物类别以泻下药、温里药、活血化瘀药、化痰药和攻毒杀虫收湿止痒药为主;性味以辛、温为主,归经以肝、脾、肺经为主。采用逐步Logistic回归分析筛选主要影响因素,结果显示归心、肺、肾、心包经以及活血化瘀药、化痰止咳药、补虚药、收涩药均是对癥瘕积聚有治疗作用的重要影响因素(回归系数>0,且P<0.01)。常用毒性药物药对有巴豆-硇砂、巴豆-乌头、巴豆-芫花;网络聚类高频毒性中药共得到8个新的中药组合:甘遂、京大戟、芫花、巴豆;硇砂、干漆、轻粉;斑蝥、芫青;全蝎、蜈蚣、朱砂、雄黄;半夏、苦杏仁;乌头、细辛、吴茱萸、皂荚;狼毒、莽草、藜芦、附子;硫黄;网络聚类高频药物共得到6个新的中药组合:三棱、莪术、青皮、陈皮、木香、槟榔、丁香、枳壳、牵牛子、神曲;当归、川芎、桃仁、香附;大黄、鳖甲;茯苓、人参、白术、厚朴、甘草、皂荚、乌头、肉桂、干姜、附子、吴茱萸;半夏;麝香、朱砂、硇砂、干漆、巴豆、芫花。结论毒性药物在癥瘕积聚治疗中占比巨大,主要治法为泻下消积软坚、健脾温阳、利痰散结,并以活血/破血消癥贯穿其中。

Objective To explore the medication rules for the treatment of abdominal mass with toxic medicine based on the theory of“treating poison with poison”by literature review.Methods The prescriptions for abdominal mass recorded in Dictionary of Traditional Chinese Medicine Formulae were collected and sorted,and then a database of the prescription was established.The statistical analysis was carried out for the medication frequency of all of the herbs and the toxic herbs in the included prescriptions for abdominal mass,and the distribution of the medication frequency,therapeutic actions,nature,taste,meridian tropism of toxic herbs in single prescription.Multivariate analysis was performed for exploring the characteristics of the Chinese herbs.Apriori association rules were used for modeling analysis,Cytoscape 3.9.1 was used to construct the core complex network of Chinese medicine,and IBM SPSS Statistics 26 was used for systematic cluster analysis of medicine in the core network.Results A total of 607 prescriptions and 485 herbs were included for the analysis.There are 460 prescriptions containing toxic herbs,accounting for 75.78%.There are 34 herbs with the frequency≥50 times,which covered 11 toxic herbs(accounting for 32.35%).About 4/5 of the prescriptions contain toxic drugs,and about 1/5 prescriptions contain≥50%toxic drugs in single prescription.The toxic drugs can be mainly classified into the categories of purgative medicines,interior-warming medicines,medicines for activating blood and removing stasis,medicines for resolving phlegm,and medicines for removing toxin,killing parasites,astringing dampness and relieving itching.The properties of the toxic drugs are characterized by being pungent and warm,and mainly have the meridian tropism of liver,spleen,and lung.The multiple stepwise logistic regression showed that the primary influencing factors for the treatment of abdominal mass were meridian tropism of heart,lung,kidney and pericardium,medicines for activating blood and removing stasis,medicines for resolving phlegm and easing cough,medicines for supplementing deficiency,and medicines for inducing astringency(regression coefficient>0,and P<0.01).The commonly-used herbal pairs of toxic drugs were Fructus Crotonis-Sal Ammoniacus,Fructus Crotonis-Radix Aconiti,and Fructus Crotonis-Flos Genkwa.The network clustering results for high-frequency toxic drugs presented 8 herbal groups:Radix Kansui,Radix Euphorbiae Pekinensis,Flos Genkwa,Fructus Crotonis;Sal Ammoniacus,Resina Toxicodendri,Calomelas;Mylabris,Lytta;Scorpio,Scolopendra,Cinnabaris,Realgar;Rhizoma Pinelliae,Semen Armeniacea Amarum;Radix Aconiti,Herba Asari,Fructus Evodiae,Fructus Gleditsiae Abnormalis;Radix Euphorbiae Ebracteolatae,Folium Illicii Lanceolati,Rhizoma Veratri,Radix Aconiti Lateralis Preparata;Sulfur.The network clustering results for high frequency drugs presented 6 herbal groups:Rhizoma Sparganii,Rhizoma Curcumae,Fructus Aurantii,Pericarpium Citri Reticulatae Viride,Pericarpium Citri Reticulatae,Radix Aucklandiae,Semen Arecae,Flos Caryophylli,Fructus Aurantii,Semen Pharbitidis,Massa Medicata Fermentata;Radix Angelicae Sinensis,Rhizoma Chuanxiong,Semen Persicae,Rhizoma Cyperi;Radix et Rhizoma Rhei,Carapax Trionycis;Poria,Radix Ginseng,Rhizoma Atractylodis Macrocephalae,Cortex Magnoliae Officinalis,Radix Glycyrrhizae,Fructus Gleditsiae Abnormalis,Radix Aconiti,Cortex Cinnamomi,Rhizoma Zingiberis,Radix Aconiti Lateralis Preparata,Fructus Evodiae;Rhizoma Pinelliae;Moschus,Cinnabaris,Sal Ammoniacus,Resina Toxicodendri,Fructus Crotonis,Flos Genkwa.Conclusion Toxic drugs account for a large proportion in the prescriptions for the treatment of abdominal mass,and mainly have the actions for purgation,removing mass and softening hardness,invigorating spleen and warming yang,removing phlegm and dissipating mass.The therapies of promoting blood circulation,removing blood stasis,and resolving mass should be used through the course of treatment.