中药药理与临床2025，Vol.41Issue(10)：45-51,7.
不同剂量丹红注射液干预脑缺血再灌注损伤的核心代谢模块识别及量效机制研究
Identification of Core Metabolic Modules and Dose-Response Mechanism of Danhong Injection at Different Doses in Intervention of Cerebral Ischemia-Reperfusion Injury
摘要
Abstract
Objective:To apply the core module identification method of modular pharmacology to reveal the key dose-response mechanism of Dan-hong(丹红)Injection in ischemia-reperfusion injury at the targeted metabolomics level.Methods:Based on targeted metabolomics data ob-tained from previous studies on the intervention of different doses of Danhong Injection in cerebral ischemia-reperfusion injury,expression data of 41 targeted metabolites related to cerebral infarction were analyzed in five groups,including model control group and Danhong Injection groups at doses of 1,2.5,5,and 10 mL/kg.Using the Module Pharmacology Platform(http://112.86.129.72:48081/#/login),metabolite weighted co-expression networks were constructed for the four Danhong Injection dose groups.Through comprehensive comparison with the model control group,modules meeting the criteria of Zsummary(Z value)<2,smallest module eigengene(ME)value,and rank sum ratio(RSR)were identified as differential metabolic modules.The module with the smallest RSR value was further designated as the core metabolic module associated with the intervention of Danhong Injection in cerebral ischemia-reperfusion injury,and the metabolite with the smallest RSR value within this module was identified as the key metabolite.Pathway enrichment analysis of the core metabolic modules was conducted on the MetaboAnalyst 6.0 platform.Results:In the weighted co-expression networks of metabolites from the Danhong Injection 1,2.5,5,and 10 mL/kg groups,4,4,5,and 3 metabolic modules were identified,respectively.Compared with the model control group,no differential mod-ules were found in the 1 mL/kg group,while two differential modules were identified in each of the 2.5 mL/kg and 5 mL/kg groups,and one core module was determined for each group.The core module of the 2.5 mL/kg group was Module 2,with four key targeted metabolites doco-sahexaenoic acid,guanidinoacetate,creatine,and tyramine.The core module of the 5 mL/kg group was Module 4,with two key targeted metab-olites L-homocysteine and guanidinoacetate.In the 10 mL/kg group,which had the best therapeutic effect,only one differential module was i-dentified,which was also designated as the core metabolic module(Module 0).This module contained 13 metabolites,among which three key metabolites,i.e.,L-tyrosine,cystathionine,and L-aspartate,were identified,all of which are closely related to cerebral ischemia.The core modules of the 2.5,5,and 10 mL/kg groups were enriched in 7,3,and 6 significant key metabolic pathways,respectively,forming a metabolic network of"nitrogen metabolism-arginine biosynthesis-arginine and proline metabolism-alanine,aspartate,and glutamate metabolism-glycine,serine,and threonine metabolism".The 2.5 mL/kg group mainly acted on the upstream part of the network,the 10 mL/kg group mainly acted on the downstream part,and the 5 mL/kg group intersected with the intervention pathways of both the 2.5 mL/kg and 10 mL/kg groups,ser-ving as a bridge between them.Conclusion:Danhong Injection may improve ischemia-reperfusion injury primarily by regulating the complex metabolic network of"arginine biosynthesis-arginine and proline metabolism-alanine,aspartate,and glutamate metabolism-glycine,serine,and threonine metabolism".This metabolic network is closely related to free radical scavenging,neuroprotection,and mitigation of brain injury.关键词
脑缺血再灌注损伤/丹红注射液/代谢组学/模块药理学/代谢网络/核心模块/自由基/神经保护/脑损伤Key words
Cerebral ischemia-reperfusion injury/Danhong Injection/Metabolomics/Modular pharmacology/Metabolic network/Core module/Free radical/Neuroprotection/Brain injury引用本文复制引用
宋祺,刘骏,侯智永,俞成诚,冷媛媛,王忠..不同剂量丹红注射液干预脑缺血再灌注损伤的核心代谢模块识别及量效机制研究[J].中药药理与临床,2025,41(10):45-51,7.基金项目
中国中医科学院科技创新工程重大攻关项目(编号:CI2021A05033&CI2023C063YLL) （编号:CI2021A05033&CI2023C063YLL）
国家十三五重大新药创制专项(编号:2017ZX09301059) （编号:2017ZX09301059）
国家十二五重大新药创制专项(编号:2011ZX09304-07). （编号:2011ZX09304-07）
