基于关联规则及复杂网络分析古医籍中乳腺癌的用药规律
Analysis of Drug Use Rule of Breast Cancer in Ancient Literature Based on Association Rules and Complex Network
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摘要: 目的 探析中医古籍文献中乳腺癌相关方剂中蕴含的乳腺癌治疗用药规律。方法 采用XMinerV2.4进行Fp-Growth算法建模进行方药数据关联分析,并采用加权有向图形式表示药物之间的配伍关系;采用LiquoriceV3.0进行Complex Network建模进行方药网络分析,对网络节点进行社团聚集分析,利用社团结构表示药物配伍关系。结果 共收集内服方剂136例,外用方剂41例。内服方核心药物是莪术、白术、当归,莪术的配伍有:三棱-莪术、莪术-淫羊藿、莪术-鹿角片、莪术-肉苁蓉、莪术-枸杞子。当归的配伍有:当归-人参、当归-防风、当归-熟地;白术的配伍有:白术-石见穿、白术-南沙参和白术-枸杞子。外用药物中枯矾-白芷、僵蚕-羌活等有关联性,同时以僵蚕为主,形成了僵蚕-羌活、僵蚕-(川乌、羌活)、僵蚕-香附等不同药对或药组。通过复杂网络分析可以看出,内服方中的核心药物群有益气温阳活血药:党参、白术、黄芪、茯苓、淫羊藿、肉苁蓉、延胡索、莪术、山茱萸;养阴解毒药:南沙参、枸杞子、石见穿、露蜂房;行气活血药:当归、郁金、香附;化痰活血药:三棱、桃仁、鹿角片、丹参、延胡索、海藻。核心药物之外的配伍分析提示有昆布-牡蛎、白芥子-鹿角胶、枳壳-厚朴、玄参-白蔹等药对。外用方中的核心药物群为活血通阳解毒药:当归、白蔹、没药、葱白;杏仁、蓖麻仁;红花-乳香。核心药物之外的配伍分析提示有活血温里止痛药:当归-川芎-草乌;祛风药:僵蚕-羌活;化痰行气药:枳壳-香附-陈皮-半夏等药对。结论 运用关联规则与复杂网络的方法分析古籍文献中乳腺癌的用药规律,可为探讨古代该病的病机特点及临床治疗提供参考,开拓当代临床医生的治疗思路,结合分析结果,可将其中的典型药对尤其是当代临床少见的药对,在乳腺癌复发转移而常规治疗乏效时使用,为乳腺癌的现代临床研究提供思路与方向。Abstract: OBJECTIVE To explore the drug use rule of breast cancer in ancient medical literature on the basis of association rules and complex network. METHODS XMinerV2.4 was used to mold Fp-Growth algorithm for correlation analysis of prescription data, and weighted directed graph was used to represent the compatibility relationship between drugs. LiquoriceV3.0 was used to model the complex Net-work for network analysis of drugs, and the network nodes were analyzed for community aggregation, and the community structure was used to express the drug compatibility relationship. RESULTS 136 cases of oral prescriptions and 41 cases of external prescriptions were collected. The core drugs of the oral administration are e zhu (Rhizoma Curcumae), bai zhu (angelica) and dang gui (Radix Angelicae Sensis). The compatibility of e zhu (Rhizoma Curcumae) includes san leng (Rhizoma Sparganii) - e zhu (Rhizoma Curcumae), e zhu (Rhizoma Curcumae) - yin yang huo (Herba Epimedii), e zhu (Rhizoma Curcumae)- lu jiao pian (Cornu Cervi Tablets), e zhu (Rhizoma Curcumae) - rou cong rong (Cistanchis Herba), and e zhu (Rhizoma Curcumae)- gou qi zi (Fructus Lycii). The compatibility of dang gui (Radix Angelicae Sensis) is: dang gui (Radix Angelicae Sensis) - ren shen (Ginseng), dang gui (Radix Angelicae Sensis) - fangfeng (Divaricate Saposhnikovia), dang gui (Radix Angelicae Sensis) - shu di (Rehmannia Glutinosa); The compatibility of bai zhu (Angelica) is: bai zhu (Angelica) - shijianchuan, bai zhu (Angelica) - nan sha shen (Glehnia Root) and bai zhu (Angelica) - gou qi zi (Fructus Lycii). The correlation between ku fan (Dried Alum) and bai zhi (Angelica Dahurica) is the highest among the external medicines, and at the same time, jiang can (Bombyx Batryticatus) is the main medicine, forming different medicine pairs or groups such as jiang can (Bombyx Batryticatus) - qiang huo (Notopterygium Root), jiang can (Bombyx Batryticatus) - (chuan wu (monkshood), qiang huo (Notopterygium Root)), jiang can (Bombyx Batryticatus) - xiang fu (Nutgrass Galingale Rhizome), etc. Through complex network analysis, it can be seen that the core drug group in the oral prescription is beneficial to warming yang and activating blood: dang shen (Radix Codonopsis), bai zhu (Rhizoma Atractylodis Macrocephalae), huang qi (Radix Astragali), fu ling (Poria), yin yang huo (Herba Epimedii), rou cong rong (Herba Cistanches), yan hu suo (Rhizoma Corydalis), e zhu (Rhizoma Curcumae), shan zhu yu (Fructus Corni); Nourishing yin and resolve toxin: nan sha shen (Radix Adenophorae), gou qi zi (Fructus Lycii), shi jian chuan (Radix Clematidis), and lu feng fang (Nidus Vespae); Moving qi and activating blood herbs: dang gui (angelica), yu jin (Curcuma Aromatica) and xiang fu (Nutgrass Galingale Rhizome); Dissolving phlegm and quickening blood herbs: san leng (Sparganium), tao ren (Peach Kernel), lu jiao pian (Cornu Cervi Slice), dan shen (Salvia Miltiorrhiza), yan hu suo (Rhizoma Corydalis) and hai zao (Seaweed). The compatibility analysis outside the core drugs suggested that there were drug pairs such as kun bu (Kelp) - mu li (Oyster), bai jie zi (Mustard Seed) - lu jiao jiao (Antler Glue), zhi qiao (Bitter Orange) - hou po (Magnolia Bark), xuan shen (Figwort) - bai lian (Ampelopsis), etc. The core medicine in the external prescription is the antidote for promoting blood circulation and removing yang: dang gui (Radix Angelicae Sinensis), bai lian (Radix Ampelopsis), mo yao (Myrrha), ru xiang (Olibanum), cong bai (Bulbus Allii Fistulosi), xing ren (Semen Armeniacae Amarum), bi ma ren (Castor Bean) and hong hua (Flos Carthami). Analysis of compatibility outside the core drugs suggests that there are pain relievers for promoting blood circulation and warming the interior: dang gui (Radix Angelicae Sinensis), chuan xiong (Rhizoma Chuanxiong), cao wu (Radix Aconiti Kusnezoffii); Dispersing wind medicine: jiang can (Bombyx Batryticatus), qiang huo (Rhizoma et Radix Notopterygii); Resolving Phlegm and moving qi herbs: zhi qiao (Fructus Aurantii), xiang fu (Rhizoma Cyperi), chen pi (Pericarpium Citri Reticulatae), ban xia (Rhizoma Pinelliae), etc. CONCLUSION Using association rules and complex network methods to analyze the drug use rules of breast cancer in ancient literature can provide a reference for exploring the pathogenesis and clinical treatment of the disease in ancient times, expand the treatment thinking of contemporary clinicians, and combine the analysis results to use the typical drug pairs, especially those rare in contemporary clinical practice, when the conventional treatment for breast cancer recurrence and metastasis is ineffective, thus providing ideas and directions for modern clinical research of breast cancer.