基于数据挖掘和网络药理学的中医药治疗支气管哮喘的用药规律和作用机制分析

Medication Regularity and Mechanism of Traditional Chinese Medicine in the Treatment of Bronchial Asthma Based on Data Mining and Network Pharmacology

目的:探讨中医药治疗支气管哮喘的组方规律,预测核心药物潜在作用机制,以期为后续实验研究及临床应用提供依据与参考。方法:检索中国知网、万方数据库和维普数据库中采用中药复方治疗支气管哮喘的临床研究文献,对中药处方进行频次统计、关联规则分析,探究支气管哮喘的组方规律,并在此基础上以网络药理学策略,筛选高频药物核心靶点,通过基因本体功能富集分析和京都基因与基因组百科全书通路富集分析,研究药物对疾病的潜在作用靶点和通路,以期阐明其作用机制。结果:共纳入448项研究,包含459首处方、210味中药;其中,化痰止咳平喘药(占28.70%,1 413次/4 924次)和补虚药(占21.83%,1 075次/4 924次)应用较多,以温性(占49.31%,2 483次/5 035次)、辛味(占29.75%,2 295次/7 713次)为主,归经以入肺经(占29.08%,3 608次/12 408次)最多;关联分析得到高频药对与高频角药各10组。麻黄为治疗支气管哮喘的核心药物,其与支气管哮喘共有147个交集靶点,主要有白天竺葵苷元、草本菌素和无色矢车菊素等23种活性成分,核心靶点为热休克蛋白90AA1、肿瘤蛋白p53和JUN等,主要通路为癌症信号通路、脂质与动脉粥样硬化通路、糖尿病并发晚期糖基化终末产物(AGE)-AGE受体信号通路等。结论:中医药治疗支气管哮喘注重清肺化痰、止咳平喘及健脾益肾,兼顾解表与清热类药物的应用;高频药物麻黄的潜在靶点和作用机制主要参与药物的反应、基因表达的正向调节及凋亡过程的负调控等生物过程,发挥治疗作用。

OBJECTIVE:To probe into the prescription rule of traditional Chinese medicine in the treatment of bronchial asthma and predict the potential mechanism of core drugs,so as to provide basis and reference for the follow-up experimental research and clinical application.METHODS:Clinical literature on the treatment of bronchial asthma with traditional Chinese medicine compounds were retrieved from CNKI,Wanfang Data and VIP database.The frequency statistics and association rule analysis of traditional Chinese medicine prescriptions were carried out.Prescription rule of bronchial asthma was explored.On this basis,the core targets of high frequency drugs were screened by network pharmacology strategy.Through functional enrichment analysis of Gene Ontology and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes,the potential targets and pathways of drug action on diseases were studied in order to clarify the mechanism of action.RESULTS:A total of 448 studies were enrolled,including 459 prescriptions and 210 traditional Chinese medicines.Among them,drugs for resolving phlegm,relieving cough and asthma(28.70%,1413 times/4924 times)and tonic drugs(21.83%,1075 times/4924 times)were widely used.The main flavors were warm(49.31%,2483 times/5035 times)and pungent(29.75%,2295 times/7713 times),and the meridians were lung meridian(29.08%,3608 times/12408 times).Correlation analysis showed that there were 10 groups of high-frequency drug pairs and 10 groups of high-frequency angular drugs.Ephedra Herba was the core drug for the treatment of bronchial asthma,which had 147 intersection targets with bronchial asthma,mainly including 23 active components such as leucopelargonidin,herbacetin and leucocyanidin.Core targets were HSP90AA1,tumor proteins p53 and JUN,and the main pathways were cancer signaling pathway,lipid and atherosclerosis pathway,and diabetes complicated with advanced glycation end products(AGE)and the receptors.CONCLUSIONS:Traditional Chinese medicine in the treatment of bronchial asthma should focus on clearing lung-heat and eliminating phlegm,relieving cough and asthmatic asthma,strengthening spleen and kidney,and taking into account the application of exterior-relieving and heat-clearing drugs.The potential targets and mechanisms of Ephedra Herba are mainly involved in drug reaction,positive regulation of gene expression and negative regulation of apoptosis.