基于网络药理学探讨左归丸“补肾生髓成肝”的疗效机制  

Molecular mechanism research of Zuogui Pill about “tonifying kidney to promote liver regeneration and repair by effecting stem cells and their microenvironment” by using the network pharmacology method

作　　者：高翔[1,2] 叶之华[1,2] 戴玲[3] 李瀚旻[1,2] GAO Xiang1,2,YE Zhihua1,2,DAI Lin3,LI Hanmin1,2(1. Institute of liver disease, Hubei Provincial Hospital of Traditional Chinese Medicine （ Wuhan Hubei, 430061 ） China)

机构地区：[1]湖北省中医院肝病研究所,湖北武汉430061 [2]湖北省中医药研究院中医基础理论研究所 [3]湖北中医药大学

出　　处：《中西医结合肝病杂志》2018年第2期96-100,共5页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：国家自然科学基金(No.81603484,81703912,81373513)

摘　　要：目的:利用网络药理学方法探讨左归丸"补肾生髓成肝"的疗效机制。方法:采用中药系统药理学数据库和分析平台(TCMSP)和中药分子机制生物信息学分析工具(BATMAN-TCM)筛选左归丸的药效活性成分和潜在作用靶点,利用生物学信息注释数据库(DAVID)和KEGG通路数据库(KEGG PATHWAY Database)分析靶点基因功能分类及其涉及的信号通路。利用蛋白质相互作用数据库(STRING Database)构建靶点基因编码蛋白质的相互作用网络模型。结果:通过TCMSP和BATMAN-TCM筛选左归丸药效活性成分65个、潜在靶点基因351个,靶点基因功能包括药物反应、乙醇应答、凋亡过程及正负调控、细胞增殖及正负调控、衰老、信号转导、基因转录调控等生物学过程,涉及癌症相关通路、乙型肝炎、前列腺癌、HIF-1信号通路、TNF信号通路等32条信号通路,根据蛋白质相互作用关系确定45个左归丸药效活性成分关键靶点。结论:左归丸"补肾生髓成肝"的疗效机制可能是其药效活性成分通过靶基因-信号通路网络调节药物、乙醇及病毒因素等引起的肝组织应答,动态调节肝组织细胞增殖/凋亡,多层次、多途径实现减轻组织损伤、优化肝脏再生修复。Objective： This paper was using the network pharmacology method to explore the molecular mechanism of Zuogui Pill about＂tonifying kidney to promote liver regeneration and repair by effecting stem cells and their microenvironment＂. Methods： We screened active ingredient and its potential targets of Zuogui Pill by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（ TCMSP） and Bioinformatics Analysis Tool for Molecular mech ANism of Traditional Chinese Medicine（ BATMAN-TCM）. The entire target genes were clustered by gene function annotation using the Database for Annotation,Visualization and Integrated Discovery（ DAVID）,and pathway enrichment were performed in KEGG PATHWAY Database. The interaction network model of target gene coding protein was constructed by using the protein-protein interaction database（ STRING Database）. Results： There were 65 active ingredients and 351 potential target genes screened through TCMSP and BATMAN-TCM. Target gene function annotation results shows that the biological process ontology included response to drug,response to ethanol,positive and negative regulation of apoptotic process,positive and negative regulation of cell proliferation,aging,signal transduction,gene transcription regulation and so on. KEGG pathway enrichment analysis shows that target genes involved 32 pathways,such as pathways in cancer,hepatitis B,prostate cancer,HIF-1 signaling pathway,TNF signaling pathway and more.According to the protein-protein interaction relationship,45 genes were determined as the key targets of Zuogui Pill active ingredients. Conclusion： The molecular mechanism of Zuogui Pill regulating liver regeneration perhaps was reduce tissue damage and optimize regeneration through multi-level and multi-pathway of the targets-pathway network,for instance,to regulate the response of liver tissues caused by drugs,ethanol and viral factors,and dynamically regulate the proliferation/apoptosis of liver tissue cells.

关 键 词：网络药理学 左归丸 补肾生髓成肝 肝再生 

分 类 号：R285.5[医药卫生—中药学]