天然产物研究与开发 ›› 2022, Vol. 34 ›› Issue (11): 1947-1958.doi: 10.16333/j.1001-6880.2022.11.016

• 数据研究 • 上一篇    下一篇

基于数据挖掘和网络药理学研究强直性脊柱炎的用药规律及高频药物组合的分子作用机制

姜平1,2,何东仪1,2*   

  1. 1上海中医药大学光华临床医学院,上海 201203;2上海中医药大学附属光华医院风湿免疫科,上海 200050
  • 出版日期:2022-11-25 发布日期:2022-11-25
  • 基金资助:
    国家自然科学基金面上项目(82074234);2021年度上海中医药大学“研究生创新培养专项”(Y2021076)

Study on the drug rule of prescriptions and molecular mechanism of high frequency drug pairs in the treatment of ankylosing spondylitis based on data mining and network pharmacology

JIANG Ping1,2,HE Dong-yi1,2*   

  1. 1Guanghua Clinical Medical College,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;2Department of Rheumatology,Shanghai Guanghua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200052,China
  • Online:2022-11-25 Published:2022-11-25

摘要:

基于数据挖掘及网络药理学分析方法,总结上海中医药大学附属光华医院风湿免疫科医师运用中药治疗强直性脊柱炎(ankylosing spondylitis,AS)的用药规律。并对出现频率最高的药对进行网络药理学分析,进一步阐释其药理作用机制,为中药治疗AS提供一定的参考。本研究以上海中医药大学附属光华医院为主要研究中心,采用横断面调查研究方法,对就诊于光华医院风湿免疫门诊及住院部的AS患者进行信息采集,收集患者的基本信息、中药治疗处方等数据资料,并依托现代计算机信息技术,采用数据挖掘方法进行分析,并对得到的高频药对进行网络药理学分析。收集到中药处方200个,统计中药236味,使用频率≥1%的中药有狗脊、白术、独活等28味,主要是补虚药、清热药、活血化瘀药和祛风湿药;关联规则后得到频数≥40的药物组合33个,其中狗脊-续断排名最高。网络药理学分析结果显示狗脊-续断共含有12个有效成分,对应作用蛋白430个;药物作用于疾病的主要基因包括TNF、EGFR、VEGFA、STAT3、HSP90AA1、PTGS2、MMP2、MMP9、IL2等。基因本体论(GO)生物过程分析和京都基因和基因组百科全书(KEGG)通路分析显示主要参与炎症调控反应和配体激活的转录因子活性等多项进程,并通过癌症通路、Toll样受体信号通路、神经营养素信号通路和T细胞受体信号通路等多条通路作用于AS。上海中医药大学附属光华医院在治疗AS上采用补虚强脊为主,兼以清热、活血化瘀、祛风除湿的标本兼治方法,为进一步应用中医药治疗AS提供参考;网络药理分析表明狗脊-续断中β-谷甾醇、山奈酚等成分可能通过TNF、VEGFA、STAT3、PTGS2、MMP9、IL2等靶点作用于癌症通路、Toll样受体信号通路和T细胞受体信号通路等,从而发挥治疗AS的作用。表明中医药治疗疾病具有多成分、多靶点、多通路的特点,为后续临床应用提供了理论基础。 

关键词: 数据挖掘, 聚类分析, 因子分析, 网络药理学, 强直性脊柱炎 

Abstract:

Based on the methods of data mining and network pharmacological analysis,the medication rule of rheumatism immunology physicians of Guanghua Hospital affiliated to Shanghai University of Traditional Chinese Medicine (TCM) in the treatment of ankylosing spondylitis was summarized.To explain the pharmacological mechanism,network pharmacology of the drug pairs with the highest frequency was analyzed,so as to provide some reference for the treatment of AS with TCM.This study took Guanghua Hospital affiliated to Shanghai University of TCM as the main research center,and adopted the method of cross-sectional investigation to collect the information of AS patients in the rheumatic immunology clinic and inpatient department of Guanghua Hospital.The basic information of the patients and the treatment prescription of TCM was collected.Relying on modern computer information technology,the data were analyzed by data mining.The obtained high-frequency drug pairs were analyzed by network pharmacology.200 prescriptions of TCM were collected,and 236 kinds of herbs were collected.There were 28 herbs with frequency ≥ 1%,such as Rhizoma Cibotii,Rhizoma Atractylodis Macrocephalae and Radix Angelicae Pubescentis,mainly tonifying deficiency,clearing heat,activating blood stasis and dispelling wind and dampness.After association rules,33 drug combinations with frequency ≥ 40 were obtained,of which Rhizoma Cibotii-Radix Dipsaci (RC-RD) ranked the highest.The results of network pharmacological analysis showed that there were 12 active components and 430 corresponding proteins,and the main genes included TNF,EGFR,VEGFA,STAT3,HSP90AA1,PTGS2, MMP2, MMP9,and IL2.Gene Ontology (GO) biological process analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis showed that it was mainly involved in many processes such as inflammatory regulation and ligand-activated transcription factor activity,and acts on AS through pathways in cancer,toll-like receptor signaling pathway,neurotrophin signaling pathway and T cell receptor signaling pathway.Guanghua Hospital affiliated to Shanghai University of TCM mainly adopts the methods of tonifying deficiency and strengthening spine,clearing heat,promoting blood circulation and removing blood stasis,dispelling wind and removing dampness in the treatment of AS,so as to provide reference for the further application of TCM in the treatment of AS.Network pharmacology analysis showed that β-sitosterol and kaempferol may act on TNF,VEGFA,STAT3,PTGS2,MMP9,IL2 and other targets.And they can regulate multiple pathways such as cancer signaling pathway,toll-like receptor signaling pathway and T cell receptor signaling pathway.It indicates that TCM has the characteristics of multi-components,multi-targets and multi-pathways,which provides a theoretical basis for follow-up clinical application.

Key words: data mining, cluster analysis, factor analysis, network pharmacology, ankylosing spondylitis

中图分类号:  R285