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 ›› 2016, Vol. 39 ›› Issue (12): 989-997.doi: 10.3969/j.issn.1006-2157.2016.12.005

• 科技之窗 • 上一篇    下一篇

基于共表达蛋白相互作用网络探讨川芎嗪治疗冠心病的机制*

霍梦琪,张燕玲,郑世超,乔延江#   

  1. 北京中医药大学中药信息工程研究中心 北京 100102
  • 收稿日期:2016-07-22 出版日期:2016-12-30 发布日期:2016-12-30
  • 通讯作者: 乔延江,男,博士,教授,博士生导师,E-mail:yjqiao@bucm.edu.cn
  • 作者简介:霍梦琪,女,在读硕士生
  • 基金资助:
    *国家自然科学基金项目(No. 81430094)

Mechanism of tetramethylpyrazine in treatment of coronary heart disease based on the coexpression-protein interaction network*

HUO Mengqi,ZHANG Yanling,ZHENG Shichao,QIAO Yanjiang#   

  1. Research Center of Traditional Chinese Medicine Information Engineering,Beijing University of Chinese Medicine,Beijing 100102
  • Received:2016-07-22 Online:2016-12-30 Published:2016-12-30

摘要: 目的 基于共表达蛋白相互作用网络探讨川芎嗪治疗冠心病的作用机制。方法 根据数据库(STITCH与Chemprot)检索和药效团的虚拟筛选获得川芎嗪的靶点及靶点的蛋白相互作用信息,在Cytoscape中构建川芎嗪对应靶点的蛋白相互作用网络。结合基因表达谱分别构建疾病与正常2种状态下的共表达蛋白相互作用网络,运用基于边聚类系数的快速凝聚算法(FAG-EC)和Gene Ontology(GO)富集分析对疾病状态下的共表达网络进行模块聚类和功能注解,将获得的功能模块映射到正常状态下的共表达网络,得到相对应的功能模块,并对正常和疾病状态下的功能模块进行对比分析。结果 川芎嗪主要通过调控免疫/炎症反应、细胞凋亡信号通路、血液循环、血红素代谢以及基础代谢等途径达到治疗冠心病的效果,而髓过氧化物酶(MPO)和血红素加氧酶-1(HMOX1)可能是冠心病治疗的关键靶点。结论 从分子网络水平探讨了川芎嗪治疗冠心病的作用机制和关键靶点,为其临床应用提供了依据。

关键词: 川芎嗪, 冠心病, 功能模块, 作用机制

Abstract: Objective To explore the mechanism of tetramethylpyrazine in the treatment of coronary heart disease (CHD) based on the coexpression-protein interaction network analysis. Methods The targets’ information of tetramethylpyrazine was obtained from pharmacophore-based virtual screening and database searching from STITCH & Chemprot, and the protein-protein interactions of the targets were retrieved by String database. The protein interaction network was constructed by Cytoscape. Next, the coexpression-protein interaction networks were constructed by integrating gene-expression profile under physiological and disease conditions. The modules of disease associated coexpression-protein interaction network were clustered and functional annotated based on fast agglomerate algorithm based on the edge clustering coefficients (FAG-EC) and gene ontology (GO) enrichment, by which the function modules were mapped to the coexpressin-protein interaction network under the normal physiological state to get the corresponding function modules. Then the function modules under two different conditions were compared and analyzed. Results The effect of tetramethylpyrazine on CHD was achieved by means of regulating and controlling immunological regulation or inflammatory response, cell apoptosis signaling pathway, blood circulation, heme metabolism and basal metabolism; myeloperoxidase (MPO) and hemeoxygenase-1 (HMOX1) probably were two key targets in treatment of CHD. Conclusion The mechanism and the key targets of tetramethylpyrazine in the treatment of CHD were illuminated at the molecular networks level, which could provide reference for clinical practice.

Key words: tetramethylpyrazine, coronary heart disease (CHD), function modules, mechanism

中图分类号: 

  • R9-39