摘要
综合运用生物信息学、网络生物学等新的视角,研究醒脑静注射液的分子作用机制,揭示处方各药配伍机制科学内涵。该研究借助整合药理学平台V1.0软件的分析功能构建＂药材-化合物-靶点＂网络、并解析各药在处方中的作用机制信息。从该处方中筛选到795个靶点,建立＂药物靶标-疾病靶标＂网络后包含302个关键靶标,富集分析显示与MAPK cascade,negative/positive regulation of apoptotic process等生物功能和PI3K/AKT,neurotrophin等信号通路有关。不同药物的靶点功能相似,相互补充,协同归属于共同的信号通路,具有协同增效作用。通过对＂核心成分-关键靶标-主要通路＂网络分析,麝香在处方的25个核心成分中占据15个,29个核心靶点中麝香涉及25个,其中SLC1A2,AR,PGR,CAT,NMDA受体等靶点与脑梗死相关。麝香、栀子和冰片的配伍对细胞凋亡可以起到双向调控作用,麝香和栀子协同作用于Ras信号通路,提示麝香发挥君药作用,其他3味药物起协同辅助作用。该研究为醒脑静注射液治疗脑梗死的配伍机制提供了生物信息学支持,为该处方的组方合理性提供了理论支持。
This paper aimed to explore the molecular mechanism of Xingnaojing injection and its scientific connotation of compatibility mechanism from a new perspective on bioinformatics and network biology. Based on the analysis function of intergrative pharmacology platform V1. 0,the compatibility mechanism of this prescription was investigated by constructing the herbs-compounds-targets network. Seven hundreds and ninety-five targets from the prescription were screened out,then 302 hub nodes were included in drug targets-disease targets network. Enrichment analysis showed that it was related to MAPK cascade,negative/positive regulation of apoptotic process and other biological functions as well as PI3 K/AKT,neurotrophin and other signal pathways. The target functions of different drugs were similar,complementing each other,and belonging to the common signaling pathway with asynergistic effect. Based on analysis of core components-key targets-main pathway network,among totally 25 core components and 29 key targets,musk had 15 and 25 respectively. SLC1 A2,AR,PGR,CAT,NMDA receptors and other targets were associated with cerebral infarction. Musk,gardenia and borneol compatibility can play a bidirectional regulation of apoptosis; musk and gardenia showed synergistic effect on Ras signaling pathway,indicating that musk was the main ingredient of the injection and the other three drugs played the role of assistance. This study could not only provide the bioinformatics support in compatibility mechanism of Xingnaojing injection,but also provide theoretical support for its formula rationality.
作者
宋福江
范斌
孙健
SONG Fu-jiang;FAN Bin;SUN Jian(Shandong University of Traditional Chinese Medicine, Ji＇nan 250355, China;State Key Laboratory Breeding Base of Dao-di Herbs, Experimental Research center China Academy of Chinese Medical Sciences, Beijing 100700, China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2018年第7期1366-1372,共7页
China Journal of Chinese Materia Medica
基金
国家自然科学基金项目(81102672)
中央级公益性科研院所基本科研业务费专项(ZZ2016013)
中央本级重大增减支项目(2060302)
关键词
醒脑静注射液
网络药理学
脑梗死
配伍机制
Xingnaojing injection
network pharmacology
cerebral infarction
compatibility mechanism
