基于内源性代谢物挖掘黄连苦寒药性的生物学表征规律  

Exploration on biological characterization of the bitter-cold property of Coptidis Rhizoma based on endogenous metabolites

作　　者：刘霜 张淼[1] 孟晶[2] 高旅 宋琦 窦宝凯 谢冉 刘星 臧梦楠 旺建伟[1] 隋峰[2] LIU Shuang;ZHANG Miao;MENG Jing;GAO LV;SONG Qi;DOU Baokai;XIE Ran;LIU Xing;ZANG Mengnan;WANG Jianwei;SUI Feng(School of Basic Medicine,Heilongjiang University of Chinese Medicine,Harbin 150040,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]黑龙江中医药大学基础医学院,哈尔滨150040 [2]中国中医科学院中药研究所,北京100700

出　　处：《中华中医药杂志》2025年第1期195-202,共8页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：中国中医科学院科技创新工程项目(No.CI2021A03803);国家自然科学基金面上项目(No.82173998,No.82374057)。

摘　　要：目的:采用代谢组学技术观察黄连(Coptidis Rhizoma)对小鼠血清内源性代谢物的影响,寻找其相关生物标志物和可能表征黄连临床治疗作用的代谢途径及其相关靶点,探讨其发挥疗效的分子机制。方法:小鼠随机分为对照组和黄连组,分别灌胃蒸馏水和黄连水煎液,采用超高效液相色谱串联质谱(UPLC-MS/MS)技术分析两组小鼠血样,采用主成分分析、偏最小二乘判别分析、正交偏最小二乘判别分析等方法,筛选差异代谢物并进行代谢通路分析;使用Cytoscape及Metscape软件对差异代谢物进行网络模块化分析,筛选可能的作用靶点。结果:数据模式识别显示黄连组与对照组血清样本完全分离:共筛选出20个差异代谢物;通过通路分析,得出19条相关通路,包括亚油酸代谢,花生四烯酸代谢,甘氨酸、丝氨酸和苏氨酸代谢,柠檬酸循环(TCA循环)和糖酵解/糖异生等;网络模块化分析共得到18个模块,其中花生四烯酸代谢通路和亚油酸代谢通路是最大的2个模块;在整个模块中只有花生四烯酸、亚油酸节点度均大于均值,涉及的通路包括花生四烯酸代谢、亚油酸代谢通路;通过筛选获得细胞色素P450(CYP450)酶系相关的26个基因。结论:黄连可能通过作用于CYP450酶系,影响花生四烯酸、亚油酸代谢途径,调控机体能量代谢,进而实现生物效应。Objective:To uncover the molecular mechanism of efficacy of Coptidis Rhizoma by observing its effects on serum metabolites in mice using metabolomics technology,as well as explore the related biomarkers,metabolic pathways and related targets that may characterize the clinical therapeutic effect of Coptidis Rhizoma.Methods:The mice were randomly divided into control group and Coptidis Rhizoma group,which were intragastrically administrated with distilled water and Coptis Rhizoma decoction,respectively.The blood samples of two groups were analyzed by UPLC-MS/MS.The analysis methods such as principal component analysis,partial least squares discrimination analysis and orthogonal partial least squares discrimination analysis were selected to screen differential metabolites and analyze metabolic pathways.In order to screen possible targets,Cytoscape and Metascape software were used to establish the network modularization analysis of differential metabolites.Results:Data pattern recognition showed that serum samples of Coptis group and control group were completely separated with 20 different metabolites screened.Through pathway analysis,19 related pathways were obtained,including linoleic acid metabolism,arachidonic acid metabolism,glycine,serine and threonine metabolism,citric acid cycle(TCA cycle) and glycolysis/gluconeogenesis.A total of 18 modules were obtained by network modular analysis,among which the arachidonic acid metabolic pathway and linoleic acid metabolic pathway were the largest two modules.In the whole module,only arachidonic acid and linoleic acid node degree is greater than the average,which involved pathways include arachidonic acid metabolism and linoleic acid metabolism pathway.The selected genes which belong to Cytochrome P450(CYP450).Conlusion:Coptis Rhizoma may regulate energy metabolism and affect metabolic pathways of arachidonic acid,linoleic acid,by acting on cytochrome P450enzymes to achieve it's biological effect.

关 键 词：黄连 内源性代谢物 代谢组学 花生四烯酸代谢 亚油酸代谢 

分 类 号：R285.5[医药卫生—中药学]