摘要
目的基于网络药理学和生物信息学方法探讨理中汤(LZT)治疗胃溃疡(GU)的分子网络调控机制。方法通过检索中药系统药理学数据库和分析平台(TCMSP)中LZT的所有成分数据,筛选并预测其入血活性成分和作用靶点;通过疾病数据库检索与GU发病相关的基因,构建LZT成分靶点与GU疾病靶点的交互网络,获得LZT治疗胃溃疡的特征性基因;通过DAVID数据库对特征性基因进行基因本体(GO)和KEGG信号通路分析,利用Cytohubba筛选出LZT治疗胃溃疡的关键靶点。结果在TCMSP中共检索出LZT的化学成分629个,根据ADME参数筛选获得入血的活性成分100个,预测靶点208个;通过疾病靶点数据库共检索到与GU发生、发展密切相关的靶点486个;运用Cytoscape筛选出LZT治疗GU的直接或间接靶点231个;GO和KEGG结果显示LZT可能通过调控Erb、JAK-STAT、FoxO、MAPK、PI3K-Akt等信号通路、细胞因子之间的相互作用等发挥治疗效应,其作用的关键靶点主要包括AKT1、EGF、ERBB2、STAT3和TP53等。结论LZT治疗GU具有多成分、多途径和多靶点的特点,其治疗GU的分子网络机制主要与调控JAK-STAT、MAPK、PI3K-Akt等信号通路和EGF、AKT1、STAT3等关键靶点密切相关。本研究可为LZT临床应用于GU的治疗提供理论依据。
Objective To explore the molecular network regulation mechanism of Lizhong Tang(LZT)in the treatment of gastric ulcer(GU)based on network pharmacology and bioinformatics.Methods By searching all components of LZT in TCMSP,screening and predicting the active ingredients and targets of LZT in blood,searching the genes related to the pathogenesis of GU through disease database,constructing the interaction network between LZT component targets and GU disease targets,and obtaining the characteristic genes of LZT in treating gastric ulcer through DAVID database.Cytohubba was used to screen out the key targets of LZT in the treatment of gastric ulcer by analyzing gene ontology(GO)and KEGG signaling pathways.Results 629 chemical constituents of LZT were retrieved in TCMSP,100 active ingredients were screened according to ADME parameters,and 208 predicted targets were obtained.486 targets closely related to the occurrence and development of GU were retrieved from the disease target database.231 direct or indirect targets of LZT for GU were screened by Cytoscape.GO and KEGG results showed that LZT might regulate Erb,JAKSTAT by controlling Erb,JAK-STAT.The key targets include AKT1,EGF,ERBB2,STAT3 and TP53.Conclusion LZT treatment of GU has the characteristics of multi-component,multi-pathway and multi-target.The molecular network mechanism of LZT treatment of GU is closely related to regulating JAK-STAT,MAPK,PI3 K-Akt signaling pathways and EGF,AKT1,STAT3 and other key targets.This study can provide a theoretical basis for the clinical application of LZT in the treatment of GU.
作者
陈小娟
曾梅艳
宋厚盼
陈新怡
何卫波
蔡雄
喻嵘
彭清华
Chen Xiaojuan;Zeng Meiyan;Song Houpan;Chen Xinyi;He Weibo;Cai Xiong;Yu Rong;Peng Qinghua(Institute of Diagnostics of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,China;College of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2020年第2期516-527,共12页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金委员会青年课题(81703920):基于TOLL样受体信号通路“危险模式”效应理论解析温中益气健脾法治疗HP相关性溃疡的分子机制,负责人:宋厚盼
湖南省自然科学基金委员会青年课题(2019JJ50442):基于miR-146b靶向调控TGF-β信号级联介导的黏膜免疫探讨黄芪建中汤治疗消化性溃疡的分子机制,负责人:宋厚盼
湖南省中医药管理局一般项目(201780):基于胞外信号调控激酶传导通路探讨脾之卫理论与肠黏膜机械屏障相关性的研究,负责人:宋厚盼。
关键词
理中汤
胃溃疡
分子机制
网络药理学
生物信息学
Lizhong Decoction
gastric ulcer
molecular mechanism
network pharmacology
bioinformatics
