基于数据挖掘和网络药理学探讨房颤的用药规律及核心药物作用机制

Prescription rules and mechanism of core drugs in the treatment of atrial fibrillation based on data mining and network pharmacology

关键词:  房颤  数据挖掘  网络药理学  用药规律

Key words:  atrial fibrillation  data mining  network pharmacology  medication rule

摘要:

[目的] 基于现代文献挖掘中医药治疗心房颤动（简称房颤）的用药规律及核心药物，并探讨核心药物的作用机制。[方法] 检索、筛选中国知网、维普、万方数据库中的文献，收集治疗房颤的中药处方，应用中医传承辅助平台软件（2.5版）对符合纳入标准的处方进行中药频次、性味、归经、四气、五味的分类统计，挖掘中药治疗房颤的用药规律，通过药物组合的关联规则分析挖掘治疗房颤的核心药物；将核心药物输入到BATMAN-TCM系统，对核心药物进行疾病富集、KEGG通路分析，绘制靶点-通路-疾病网络可视图，探析核心药物治疗房颤的作用机制。[结果] 根据纳排标准，共纳入符合条件的处方220首，涉及中药222味，药用频数≥30次的中药有24味，排名前10位的中药分别为甘草、麦冬、丹参、黄芪、五味子、酸枣仁、当归、牡蛎、党参、桂枝。药物四气以温、寒、平为主，五味以甘、苦、辛为主。归经排名前3位的是心、肝、脾。通过关联规则分析，得到处方中使用频数≥40次的药物组合13对，包含麦冬、五味子、甘草、龙骨、牡蛎、黄芪、丹参、酸枣仁、桂枝9味中药；得到药物组合规则14条，分别为：甘草、五味子->麦冬，龙骨->牡蛎，五味子->麦冬，牡蛎->龙骨，桂枝->甘草，麦冬、甘草->五味子，麦冬、五味子->甘草，麦冬->五味子，五味子->甘草，酸枣仁->麦冬，牡蛎->甘草，酸枣仁->甘草，麦冬->甘草，五味子->麦冬、甘草；挖掘出治疗房颤的核心药物为：麦冬、五味子、甘草、龙骨、牡蛎、黄芪、丹参、酸枣仁、桂枝。KEGG通路分析发现这9味核心药物的富集疾病与房颤相关的有12种，潜在信号通路36条。[结论] 临床治疗房颤药物多以益气养阴、活血安神药为主，核心药物治疗房颤的作用机制可能与丝裂原活化蛋白激酶（MAPK）信号通路、钙离子信号通路、雷帕霉素靶蛋白（mTOR）信号通路和磷脂酰肌醇激酶-蛋白激酶B（PI3K-Akt）信号通路有关。

Abstract:

[Objective] Based on the modern literatures,to explore the prescription rules and core drugs of traditional Chinese medicine (TCM) in the treatment of atrial fibrillation (AF) and to explore the action mechanism of core drugs.[Methods] The literatures in CNKI,VIP,and Wanfang databases were searched,and the prescriptions for the treatment of atrial fibrillation were collected. The TCM transmission aid platform software (version 2.5) was used to classify and count the prescriptions that met the inclusion criteria in terms of frequency,nature and flavor,meridian tropism,four properties and five flavors of TCM,to excavate the prescription rules of TCM for the treatment of atrial fibrillation,and to excavate the core drugs for the treatment of atrial fibrillation through the association rule analysis of drug combinations. The core drugs were entered into the BATMAN-TCM system,to conduct disease enrichment and KEGG pathway analysis of the core drugs,and the target-pathway-disease network was drawn to explore the action mechanism of core drugs in the treatment of atrial fibrillation.[Results] According to inclusion and exclusion criteria,a total of 220 qualified prescriptions were included,involving 222 Chinese medicine,24 Chinese medicine with a frequency of ≥ 30 times,and the top 10 Chinese medicine were glycyrrhizae radix et rhizoma,ophiopogonis radix,salviae miltiorrhizae radix et rhizoma,astragali radix,schisandrea chinensis,ziziphi spinosae semen,angelicae sinensis radix,ostreae concha,codonopsis radix,cinnamomi ramulus. Four properties were mostly warm,cold,flat;the five flavors were mostly sweet,bitter,pungent. The top three meridians are heart,liver and spleen. Through association rule analysis,13 pairs of drug combinations with the use frequency ≥ 20 times in the prescriptions were obtained,including 9 Chinese medicine:ophiopogonis radix,schisandrea chinensis,glycyrrhizae radix et rhizoma,fossilia ossis mastodi,ostreae concha,astragali radix,salviae miltiorrhizae radix et rhizoma,ziziphi spinosae semen,cinnamomi ramulus. Six drug combination rules were obtained,namely:glycyrrhizae radix et rhizoma,schisandrea chinensis->ophiopogonis radix,fossilia ossis mastodi->ostreae concha,schisandrea chinensis->ophiopogonis radix,ostreae concha->fossilia ossis mastodi,cinnamomi ramulus->glycyrrhizae radix et rhizoma,ophiopogonis radix,glycyrrhizae radix et rhizoma->schisandrea chinensis,ophiopogonis radix,schisandrea chinensis->glycyrrhizae radix et rhizoma,ophiopogonis radix->schisandrea chinensis,schisandrea chinensis->glycyrrhizae radix et rhizoma,ziziphi spinosae semen->ophiopogonis radix,ostreae concha->glycyrrhizae radix et rhizoma,ziziphi spinosae semen->glycyrrhizae radix et rhizoma,ophiopogonis radix->glycyrrhizae radix et rhizoma,schisandrea chinensis->ophiopogonis radix,glycyrrhizae radix et rhizoma. The core drugs for the treatment of atrial fibrillation were found as follows:ophiopogonis radix,schisandrea chinensis,glycyrrhizae radix et rhizoma,Longgu,ostreae concha,astragali radix,codonopsis radix,ziziphi spinosae semen,cinnamomi ramulus. KEGG pathway analysis found that the enrichment of these 9 core drugs was associated with atrial fibrillation in 12 kinds of diseases and 36 potential signaling pathways.[Conclusion] Most of the drugs used in the clinical treatment of atrial fibrillation are based on supplementing qi and nourishing yin,activating blood and tranquilizing mind. The action mechanism of the core drugs in the treatment of atrial fibrillation may be related to mitogen-activated protein kinase(MAPK) signaling pathway,calcium signaling pathway,mammalian target of rapamycin(mTOR) signaling pathway and phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) signaling pathway.