基于数据挖掘和网络药理学探讨中药治疗化疗相关性恶心呕吐的用药规律和机制

Medication rule and mechanism of traditional Chinese medicine in treatment of chemotherapy-induced nausea and vomiting:A study based on data mining and network pharmacology

目的:分析和挖掘中医药治疗化疗相关性恶心呕吐(CINV)的用药特点、潜在关联规则及配伍规律,并借助网络药理学和分子对接技术探讨高频药物干预CINV的作用机制。方法:收集中国知网(CNKI)、万方数据(WANFANG DATA)、维普中文科技期刊数据库(VIP)中2000年1月1日至2020年12月31日发表的中医药治疗CINV的随机对照文献,采用统计描述、关联规则、聚类分析等方法探讨中药治疗CINV的用药规律。利用TCMSP数据库收集相关活性成分,进行靶点预测,利用DAVID数据库进行京都基因与基因组百科全书(KEGG)通路富集分析,使用分子对接技术对核心化学成分与关键靶点进行分子对接验证。结果:共纳入符合要求的文献101篇,涉及中药141味;高频核心药物主要有甘草、半夏、茯苓、白术和陈皮,中药功效以补虚和化痰为主;关联组合提升度较高者为“半夏-大枣-甘草→生姜”等;共筛选得到核心药物活性成分131个,作用靶点151个,认为高频核心药物可能通过神经活性配体-受体相互作用、钙信号通路和5-羟色胺能突触等作用机制对CINV发挥作用。结论:中医药治疗CINV以健脾化痰止呕为法,多采用补虚药、化痰药、理气药,其中甘草、半夏、茯苓、白术、陈皮为高频核心药物,网络药理学和分子对接结果进一步验证了高频核心药物治疗CINV的微观作用机制。

Objective:To investigate the medication feature,potential association rule,and compatibility rule of traditional Chinese medicine(TCM)in the treatment of chemotherapy-induced nausea and vomiting(CINV),as well as the mechanism of action of high-frequency TCM drugs in the intervention of CINV based on network pharmacology and molecular docking.Methods:CNKI,Wanfang Data,and VIP databases were searched for randomized controlled trials on TCM in the treatment of CINV published from January 1,2000 to December 31,2020,and the methods including statistical description,association rule,and cluster analysis were used to investigate the medication rule of TCM in the treatment of CINV.TCMSP database was used to collect related active components and perform target prediction,DAVID database was used to performKyoto Encyclopedia of Genes and Genome pathway enrichment analysis,and the molecular docking technique was used to perform molecular docking validation of core chemical components and key targets.Results:A total of 101 articles meeting the inclusion criteria were included,involving 141 TCM drugs.High-frequency core drugs included Radix Glycyrrhizae,Pinellia ternata,Poria cocos,Atractylodes macrocephala Koidz.,and tangerine peel,and deficiency-tonifying and phlegm-eliminating were the main functions of TCM drugs.The combinations with a relatively high degree of association included“Pinellia ternata-jujube-Radix Glycyrrhizae-ginger”.A total of 131 active components and 151 action targets were screened out for the core drugs,and it was believed that high-frequency core drugs might exert a therapeutic effect on CINV via the mechanisms of action such as neuroactive ligand-receptor interaction,calcium signaling pathway,and 5-hydroxytaminergic synapses.Conclusion:In the treatment of CINV,TCM treatment applies the method of invigorating the spleen,removing phlegm,and arresting vomiting and often uses deficiency-tonifying,phlegm-eliminating,and Qi-regulating drugs,among which Radix Glycyrrhizae,Pinellia ternata,Poria cocos,Atractylodes macrocephala Koidz.,and tangerine peel are the high-frequency core drugs.Network pharmacology and molecular docking further validate themicroscopic mechanism of action of the high-frequencycore drugs in the treatment of CINV.