苦参治疗病毒性心肌炎的网络药理学研究  

Study of Kushen(radix sophorae flavescentis)in treatment of viral myocarditis based on network pharmacology

作　　者：袁维运 姚焕英 曹亮 张旭 邓国荣 马静 李哲[5] 王李雯[5] 张莎 YUAN Wei-yun;YAO Huan-ying;CAO Liang;ZHANG Xu;DENG Guo-rong;MA Jing;LI Zhe;WANGLi-wen;ZHANG Sha(PLA Center of TCM Internal Medicine,Xijing Hospital,Air Force Medical University,Xi’an 710032,China;Department of TCM,Tangdu Hospital,Air Force Medical University,Xi’an 710038,China;School of Basic Medical Sciences,Shaanxi University of Chinese Medicine,Xianyang 712046,China;Department of Cardiology,Second Affiliated Hospital,Shaanxi University of Chinese Medicine,Xianyang 712046,China;First School of Clinical Medicine,Shaanxi University of Chinese Medicine,Xianyang 712046,China)

机构地区：[1]空军军医大学西京医院中医科暨全军中医内科中心,陕西西安710032 [2]空军军医大学唐都医院中医科暨陕西省重点中西医结合肿瘤专科,陕西西安710038 [3]陕西中医药大学基础医学院,陕西咸阳712046 [4]陕西中医药大学第二附属医院心脏内科,陕西咸阳712046 [5]陕西中医药大学第一临床医学院,陕西咸阳712046

出　　处：《心脏杂志》2023年第2期183-190,共8页Chinese Heart Journal

基　　金：国家自然科学基金项目(81803950);国家中医药管理局中医药科学技术研究专项(GZY-KJS-2021-004);陕西省自然科学基础研究计划项目(2020JQ-863);陕西省重点研发计划项目(2021SF-413);空军军医大学第二附属医院学科创新发展计划(2021ZTXM-001);陕西省中医药管理局青年培优项目(2021-PY-004);陕西省中医药管理局中西医结合临床协作创新项目(2020-ZXY-001)。

摘　　要：目的运用网络药理学方法分析苦参治疗病毒性心肌炎(viral myocarditis,VMC)的潜在作用机制,为中药苦参的深入研究及VMC的药物研发提供参考。方法通过中药系统药理学TCMSP、TCMIP、BATMANTCM数据库检索苦参发挥药效的主要活性成分及其对应靶点,借助GeneCards、OMIM、TTD、PharmGKB等数据库整理VMC疾病治疗靶标,联合导入Venny2.1.0平台绘制韦恩图并利用Cytoscape构建疾病-成分-靶点网络图与核心基因,最后,基于共有作用靶基因进行GO功能富集和KEGG通路富集分析。结果共获得苦参主要活性成分11种,对应潜在药物作用靶点662个;与1161个VMC疾病靶标映射、信息筛选后获得27个药物-疾病关键交互靶点;拓扑分析获得排位前10的核心靶点,包括IL-6、TNF、VEGFA、STAT3、MYC、EGFR、CCND1、CASP3、MMP9、IL-2等。富集分析结果发现苦参发挥VMC治疗作用主要涉及3个生物学过程和151条潜在信号通路。结论苦参治疗VMC具有多成分、多靶点、多途径的特点,其主要通过调控IL-6、TNF、VEGFA、STAT3、MYC、EGFR等核心基因靶点,参与介导PI3K-Akt、TNF、HIF-1等信号通路治疗VMC。本研究提供了苦参治疗VMC的潜在作用机制,为其后续的药理学研究和临床应用提供指导。AIM To analyze the potential mechanism of Kushen in the treatment of viral myocarditis(VMC)by network pharmacology method to provide reference for further study of Kushen and drug development for VMC.METHODS The main active components of Kushen were collated by TCMSP,TCMIP and BATMAN-TCM databases and corresponding targets were generalized.The targets related to VMC were retrieved by GeneCards,OMIM,TTD and PharmGKB databases.Venny2.1.0 platform was imported to draw Venn diagram and Cytoscape was used to construct disease-component-target network diagram and core genes.Then,GO functional enrichment and KEGG pathway enrichment analyses were performed.RESULTS A total of 11 main active components were screened out from Kushen,corresponding to 662 potential targets.After mapping and information screening with 1161 VMC disease targets,27 drug-disease interaction targets were obtained.The top 10 core targets were obtained by topological analysis,including IL-6,TNF,VEGFA,STAT3,MYC,EGFR,CCND1,CASP3,MMP9 and IL-2.The results of enrichment analyses involved three biological processes and 151 signaling pathways.CONCLUSION The treatment of VMC by Kushen is characterized by multi-components,multi-targets and multi-pathways.However,it mainly regulates core gene targets such as IL-6,TNF,VEGFA,STAT3,MYC and EGFR and participates in mediating signal pathways such as PI3K-Akt,TNF and HIF-1 that contribute to VMC.This study provides a potential mechanism of Kushen in the treatment of VMC and provides guidance for subsequent pharmacological research and clinical application.

关 键 词：苦参 病毒性心肌炎 网络药理学 

分 类 号：R542.21[医药卫生—心血管疾病]