基于数据挖掘和网络药理学的古方治疗肺结核的用药规律及机制分析

Analysis of Drug use Law and Mechanism of Ancient prescription in the treatment of Pulmonary Tuberculosis based on data Mining and Network Pharmacology

目的通过数据挖掘方法总结古方治疗肺结核的用药规律,并初步验证和预测核心药团的潜在靶标,以探讨核心药团对治疗肺结核的作用机制。方法选取中华医典5.0系统中治疗肺结核的处方,运用Excel 2016、SPSS Modeler 15.0及SPSS Statistics 23.0等软件,进行频数分析、因子分析、关联规则分析。通过检索TCMSP、SymMap、TCM-ID、Pharmmapper、UniProt、TTD、Genecards等数据库,获得核心药团的活性成分、潜在作用靶点及肺结核相关的作用靶点;筛选David数据库,对核心药团和肺结核的作用靶点进行GO及KEGG分析;运用Cytoscape 3.6.1软件构建网络图、靶点图及预测作用靶点和主要化合物的结合度。结果共纳入749首肺结核治疗处方,合计475味中药,其中排列在前10味的高频药物分别为:甘草、人参、茯苓、当归、芍药、麦冬、生姜、白术、柴胡、生地黄,从高频药物间因子分析中提取9个公因子,经关联规则分析,设置最低条件支持度≥8%,最小规则置信度≥80%,提升度>1,得出置信度最高的核心药团为芍药-熟地黄-当归。网络药理学部分,核心药团共筛选出35个化学成分和80个潜在靶点,与肺结核相关靶点14个。通过GO分析,富集出84个生物学过程,15个细胞组成,以及32个分子功能,KEGG分析得出26条信号通路。结论古代医家在运用祖国医学治疗肺结核过程中多以补虚培元、治痨杀虫为基本治则,涉及中药以补益药和化痰止咳药为主。客观地呈现了古代医家治疗肺痨的组方用药经验,为现代临床用药提供借鉴。核心药团的化学成分、潜在靶点和通路机制与免疫调节、糖酵解、炎症反应等过程有关,且相互存在着协同作用。初步验证和预测了中医药治疗肺结核的潜在作用机制,并为后续研究从中医药提取成分治疗肺结核潜在作用机制奠定夯实的科学理论基础。

Objective To explore and analyze the drug use of ancient doctors in the treatment of pulmonary tuberculosis,and to explore the potential target of the core drug group,so as to predict the mechanism of the core drug group on the treatment of tuberculosis.Methods:The prescription for treating tuberculosis in Chinese Medical Code 5.0 system was selected,and frequency analysis,factor analysis and association rule analysis were carried out by using Excel 2016,SPSSModeler 15.0 and SPSSStatistics 23.0.By retrieving TCMSP,SymMap,TCMID,Pharmapper,UniProt,TTD,Genecards and other databases were used to obtain the active components,potential targets and related targets of the core pellets,to screen the David database,to analyze the targets of the core pellets on pulmonary tuberculosis by GO and KEGG,and to construct the network map,the target map and predict the binding degree of the main compounds by using Cytoscape 3.6.1 software.Results:a total of 749 prescriptions for pulmonary tuberculosis were included.475 kinds of traditional Chinese medicine were included,among which the top 10 kinds of high frequency drugs were Glycyrrhiza uralensis Fisch,Panax ginseng,Poria umbering,Angelica sinensis,Paeonia lactiflora,Ophiopogon japonicus,and Sheng.Ginger,Atractylodes macrocephala,Bupleurum chinense and Rehmannia glutinosa were extracted from high frequency interdrug factor analysis.Through association rule analysis,the minimum condition support≥8%,minimum rule confidence≥80%,promotion>1,it was concluded that the core drug group with the highest confidence was Paeonia lactiflora,Rehmannia glutinosa and Angelica sinensis.In the part of network pharmacology,35 chemical components and 80 potential targets were screened out,and 14 targets related to pulmonary tuberculosis were selected.Through GO analysis,84 biological processes,15 cell composition and 32 molecular functions were enriched.26 signal pathways were obtained by KEGG analysis.Conclusion:ancient doctors are using it.In the process of traditional Chinese medicine in the treatment of pulmonary tuberculosis,tonifying deficiency and nourishing yuan and controlling tuberculosis and insecticidal are the basic treatment principles,involving traditional Chinese medicine is mainly tonifying drugs and resolving phlegm and relieving cough drugs.This paper objectively presents the prescription experience of ancient doctors in the treatment of tuberculosis,and provides a reference for modern clinical drug use guidance.The chemical composition,potential targets and pathway mechanism of core pellets are related to immunomodulation,glycolysis,inflammatory reaction and so on,and there is synergistic effect between them.The potential mechanism of traditional Chinese medicine in the treatment of pulmonary tuberculosis was preliminarily verified and predicted,and the scientific theoretical basis was provided for the follow-up study of the potential mechanism of extracting components from traditional Chinese medicine in the treatment of pulmonary tuberculosis.