中国中医药信息杂志2024，Vol.31Issue(2)：130-137,8.DOI:10.19879/j.cnki.1005-5304.202303286
基于代谢组学和网络药理学探讨羟基红花黄色素A治疗脓毒症急性肝损伤作用机制
Exploration on the Mechanism of Hydroxyl Safflower Flavin A in the Treatment of Sepsis-induced Liver Injury Based on Metabolomics and Network Pharmacology
摘要
Abstract
Objective To explore the mechanism of hydroxyl safflower flavin A(HSYA)in the treatment of sepsis-induced liver injury by using metabolomics and network pharmacology.Methods A total of 50 male C57BL/6 mice were randomly divided into sham-operation group(10 mice),sepsis group(20 mice)and HSYA group(20 mice).Cecal ligation and puncture was conducted to establish the sepsis-induced liver injury mouse model.The mice in HSYA group were subcutaneously injected with HSYA after 2 hours of modeling.The content of serum inflammatory factors and liver function were detected,and the pathological changes of liver tissue were observed with HE staining,UPLC-Q-TOF-MS metabolomics was used to analyze liver tissue,screening for differential metabolites using multivariate statistical methods,network pharmacology was used to predict potential targets for HSYA treatment of sepsis-induced liver injury,and conduct GO and KEGG pathway enrichment analysis on potential targets,Metabo Analyst 5.0 database was used to match differential metabolites and potential targets between the model group and HSYA group,a targets metabolite-metabolism pathway network was constructed.AutoDock Vina software was used to perform molecular docking between HSYA and core genes,and finally RT-qPCR was used to verify the expression of core genes.Results HSYA can reduce the contents of IL-6,IL-1β and TNF-α in serum,restore liver function,and alleviate the morphological alternation in liver induced by sepsis.A total of 26 differential metabolites identified by metabolomics were screened out,including flufenamic acid,cryptolepine,opthalmic acid,fenpropathrin etc.,which were mainly involved in 5 metabolic pathways such as biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism.Network pharmacology identified 81 potential targets,2 735 items enriched in GO and 124 signaling pathways enriched in KEGG;a total of 5 differential metabolites were matched for joint analysis,corresponding to 14 targets including IL1B,STAT3,PTGS2,TP53,etc.,involved in the regulation of metabolic disorders in sepsis-induced liver injury by HSYA.Molecular docking results showed that HSYA had good binding activity to IL1B,STAT3,PTGS2 and TP53 targets.RT-qPCR results showed that HSYA could inhibit the expressions of IL1B,STAT3 and PTGS2 in liver tissue.Conclusions HSYA may inhibit the release of inflammatory cytokines,maintain metabolic homeostasis,and alleviate sepsis-induced liver injury through modulating the expressions of IL1B,STAT3,and PTGS2.关键词
脓毒症/急性肝损伤/羟基红花黄色素A/网络药理学/代谢组学Key words
sepsis/acute liver injury/hydroxy safflower flavin A/network pharmacology/metabolomics分类
医药卫生引用本文复制引用
颜诗帆,潘冰冰,余婷,侯常苗,蒋宇,陈芳,王菁菁,刘艳娟,祝益民..基于代谢组学和网络药理学探讨羟基红花黄色素A治疗脓毒症急性肝损伤作用机制[J].中国中医药信息杂志,2024,31(2):130-137,8.基金项目
国家自然科学基金(82102278) （82102278）
湖南省自然科学基金(2020JJ8010、2021JJ40292) （2020JJ8010、2021JJ40292）
湖南创新型省份建设专项(2019RS1067) （2019RS1067）
