基于数据挖掘及网络药理学研究中医药治疗男性乳房发育症的用药规律及机制

Medication rules and mechanism of TCM medicine treating gynecomastia based on data mining and network pharmacology

目的:基于数据挖掘及网络药理学总结中医药治疗男性乳房发育症的用药规律,探究核心药对的作用机制。方法:收集整理中国知网、万方数据库、维普数据库中关于中医药治疗男性乳房发育症的文献,筛选并构建数据库;运用Excel 2010、IBM SPSS Modeler 18.0、IBM SPSS Statistics 21.0软件进行数据挖掘,分析研究用药规律;并利用网络药理学方法获取核心药对有效成分、构建网络图和相关作用通路;利用SwissDock数据库对主要有效成分和核心靶点进行对接验证。结果:共纳入中药处方68首,中药135种,药性以寒、温、平为主;药味以苦、辛、甘为主;使用频数大于等于10的药物共27种。其中柴胡的使用频数最高。综合关联规则、聚类分析的结果,柴胡—白芍为中医药治疗男性乳房发育的关键药对,其主要作用成分为槲皮素、山柰酚、β-谷甾醇等。关键靶点为雌激素受体1(Estrogen Receptor 1,ESR1)、孕酮受体(Progesterone Receptor,PGR)、细胞色素P4503A4酶(Cytochrome P450 Family 3 Subfamily A Member 4,CYP3A4)、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)等。主要作用通路为类固醇激素生物合成通路、癌症通路、黏着斑信号通路、催乳素信号通路和PI3K-Akt信号通路等。分子对接结果显示,关键靶点与主要有效成分具有较好的结合活性。结论:男性乳房发育症以补肾疏肝为主要治法。方药以补虚药为核心,辅以化痰药,佐以活血理气药,其核心药对通过调控乳腺细胞增殖、血管生成、细胞凋亡等信号传导通路发挥作用。

Objective:To explore the medication rules of traditional Chinese medicine treating gynecomastia and the mechanism of the core herbals.Methods:The literature on the treatment of gynecomastia with TCM from CNKI,Wanfang Data,VIP database was collected,and the database was screened and constructed.SPSS software was used to carry out data mining,analyze the rules of research drug use,and used network pharmacology methods to obtain the effective ingredients of core drugs,and constructed network maps and related action pathways,docking of key effective compounds with core targets was verified using Swiss Dock database.Results:Totally 68 prescriptions were involved,including 135 Chinese herbal medicines.The most common drug properties were cold,warm,fat.The main tastes were pungent,bitter,sweet.27 types of Chinese herbal medicines were with the frequency≥10,including Chaihu(Radix Bupleuri)which had the highest frequency.Combining the results of association rules and cluster analysis,Chaihu-Baishao(Paeoniae Radix Alba)were the key herbal medicine pair for treatment of gynecomastia,the key compounds were quercetin,kaempferol,β-sitosterol,the key targets were ESR1,PGR,CYP3A4,VEGFA,AKT1,and the main effect pathway were Steroid hormone biosynthesis,Pathways in cancer,Focal adhesion,Prolactin signaling pathway,PI3K-Akt signaling pathway.Molecular docking results showed that the key targets had better binding activity with the key ingredients.Conclusion:Gynaecomastia is mainly treated by invigorating the kidney and draining the liver.The prescription takes tonifying deficiency drugs as the core,supplemented by phlegm resolving drugs,supplemented by blood promotting and Qi(气)regulating drugs.The core medicines exert their effects through the regulation of signaling pathways such as breast cell proliferation,angiogenesis and apoptosis.