主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

北京中医药大学学报 ›› 2019, Vol. 42 ›› Issue (8): 673-679.doi: 10.3969/j.issn.1006-2157.2019.08.011

• 临床研究 • 上一篇    下一篇

基于生物网络模块探讨慢痞消治疗慢性萎缩性胃炎的作用机制*

李园1; 丁霞2; 许爱丽3; 曹琬琛4; 李萍1; 苏泽琦4#   

  1. 1 北京中医药大学东直门医院 北京 100700;
    2 北京中医药大学中医学院;
    3 中国中医科学院望京医院;
    4 北京中医药大学北京中医研究院
  • 收稿日期:2019-03-15 出版日期:2019-08-30 发布日期:2019-09-04
  • 通讯作者: 苏泽琦,女,博士,助理研究员,主要研究方向:中西医结合防治消化系统疾病基础与临床研究,E-mail: suzeqi@bucm.edu.cn
  • 作者简介:李园,女,在读博士生
  • 基金资助:
    *国家自然科学基金重点资助项目(No.81630080),国家重点研发计划资助项目(No.2018YFC1704106),北京中医药大学基本科研业务费资助项目(No.2019-JYB-XS-135),国家自然科学基金青年资助项目(No.81703931)

Mechanism of Manpixiao in treatment of chronic atrophic gastritis based on biological network module*

Li Yuan1, Ding Xia2, Xu Aili3, Cao Wanchen4, Li Ping1, Su Zeqi4#   

  1. 1 Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China;
    2 Beijing Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China;
    3 Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China;
    4 School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
  • Received:2019-03-15 Online:2019-08-30 Published:2019-09-04
  • Contact: Su Zeqi, Ph.D., Resarch Assistant. School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11, Beishanhuan Donglu Road, Chaoyang District, Beijing 100029. E-mail: suzeqi@bucm.edu.cn

摘要: 目的 通过生物网络及模块化分析方法挖掘路志正教授临床经验方慢痞消治疗慢性萎缩性胃炎(CAG)的潜在作用靶点和信号通路,从生物信息学角度阐释其潜在作用机制。方法 综合利用中药系统药理学数据库与分析平台(TCMSP)、BATMAN-TCM、在线人类孟德尔遗传数据库(OMIM)、人类表型术语集(HPO)和DisgeNet数据库分别获得慢痞消的有效成分和对应靶点以及CAG的相关靶点;通过人类蛋白质参考数据库(HPRD)和生物通用交互数据集库(BioGRID)获取已知的蛋白相互作用关系(PPI),构建“慢痞消-CAG”的PPI网络;通过ClusterONE软件挖掘核心功能模块;采用Cluego软件对其进行基因本体论(GO)功能注释以及京都基因和基因组百科全书(KEGG)信号通路富集分析。结果 检索获得慢痞消成分对应基因1 885个,CAG相关基因209个;构建“慢痞消-CAG”PPI网络有44个节点,292条边,其中核心网络模块由31个节点构成;GO功能注释和KEGG信号通路富集分析发现慢痞消治疗CAG的作用机制可能与调控白介素17信号通路(IL-17)、炎性肠病、缺氧诱导因子-1信号通路(HIF-1)、血管内皮生长因子(UEEF)信号通路等炎症反应和肿瘤相关信号通路,以及参与细胞分化、代谢、凋亡等GO功能有关,尤其对肿瘤蛋白53(TP53)、白介素家族细胞因子、前列腺素内过氧化物合酶2(PTGS2/COX-2)、肿瘤坏死因子-α(TNF-α)、血管内皮生长因子A(VEGFA)和表皮生长因子受体(EGFR)等靶点具有重要调节作用。结论 慢痞消可能通过调节免疫炎性反应和血管内皮生长因子等改善胃内微环境,发挥治疗CAG和控制慢性胃炎恶性转化的作用。本研究一方面为明确慢痞消的药理、药效机制提供了有益探索;一方面也为阐释名医经验方的作用机制研究提供了思路和方法学借鉴。

关键词: 慢性萎缩性胃炎, 慢痞消, 生物网络, 靶点

Abstract: Objective To discover the potential effect targets and signaling pathway of Manpixiao (MPX), an experiential formula of Professor Lu Zhizheng’s for chronic atrophic gastritis (CAG) through biological network and modular analysis, and explain its potential effect mechanism at point of bioinformatics. Methods The active principles of MPX and of MPX-corresponded target and CAG-related target were obtained by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), BATMAN-TCM, Online Mendelian Inheritance in Man (OMIM), Human Phenotype Ontology (HPO) and DisgeNet Database. The known protein-protein interaction (PPI) was obtained through Human Protein Reference Database (HPRD) and Biological General Repository for Interaction Datasets (BioGRID) for establishing MPX-CAG PPI network. The core functional modules were excavated by using ClusterONE software. Cluego software was used for functional explanation of gene ontology (GO) of the modules, and Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for enrichment analysis of signaling pathway of the modules. Results There were 1885 MPX-corresponded genes and 209 CAG-related genes obtained after retrieving databases. There were 44 nodes and 292 edges for establishing MPX-CAG PPI network, among them there were 31 nodes for establishing core network modules. The results of GO functional explanation and KEGG signaling pathway enrichment analysis showed that the mechanism of MPX in CAG treatment might be related some signaling pathways related to inflammatory reactions and tumors including to IL-17 signaling pathway, inflammatory bowel disease, HIF-1 signaling pathway and VEGF signaling pathway. MPX might take part in GO-related differentiation, metabolism and apoptosis, especially it had important relative effects on targets of tumor protein 53 (TP53), interleukin family cytokines, PTGS2/COX-2, tumor necrosis factor-α (TNF-α), vascular endothelial growth factor A (VEGF-A) and epidermal growth factor receptor (EGFR). Conclusion MPX can alleviate gastric microenvironment possibly through regulating immune inflammatory reactions, gastric acid secretion and VEGF, and play a role in CAG treatment and control of CAG malignant transformation. The study provides a useful exploration on the pharmacological and pharmacodynamic mechanism of MPX. On the other hand, it also provides research ideas and methodology reference for explaining the effect mechanism of famous physicians’ experience formulas.

Key words: chronic atrophic gastritis, Manpixiao, biological network, target

中图分类号: 

  • R256.3