基于LC-MS分析解毒化瘀颗粒对急性肝衰竭大鼠的尿液代谢组学的影响  

Analysis of Urine Metabonomics of Acute Liver Failure Rats Treated with Jieduhuayu Granule Based on LC-MS

作　　者：龙富立[1] 林镛 冯逢 彭子明 张建玲 曹音[1] 毛德文[1] 韦艾凌[1] LONG Fu-li;LIN Yong;FENG Feng;PENG Zi-ming;ZHANG Jian-ling;CAO Yin;MAO De-wen;WEI Ai-ling(Guangxi University of Chinese Medicine,Nanning Guangxi 530200,China)

机构地区：[1]广西中医药大学,广西南宁530200

出　　处：《时珍国医国药》2021年第7期1551-1555,共5页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81760844,81960841);国家科技重大专项(2018ZX10725505-001-011);广西科技计划项目(2018GXNSFGA281002,桂科AD17129001);广西中医基础研究重点实验室(17-259-49-04);广西一流学科(中医学)建设开放课题(2019XK023);广西中医药大学研究生教育创新计划项目(YCSY2018026,YCBSY2020002)。

摘　　要：目的基于代谢组学研究策略,研究急性肝衰竭大鼠尿液中代谢物变化,探寻解毒化瘀颗粒拮抗ALF大鼠可能的疗效机制。方法将18只大鼠随机分为3组,每组各6只,分别为正常组、模型组(ALF组)和治疗组(解毒化瘀组)。建立ALF模型后,采用液相色谱-质谱联用(LC-MS)的代谢组学方法对大鼠尿液样本进行检测,结合质谱信息和公共数据库检索对检测到的代谢物进行鉴定,用主成分分析(PCA)和偏最小二乘法判别分析(PLS-DA)分析组间代谢产物差异。结果正常组、模型组、治疗组的代谢轮廓有明显差异,筛选并鉴定出组间具有显著性差异的生物标记物8个,其中受治疗组干预后回调的生物标记物6个(VIP>1,P<0.05)分别是黄嘌呤核苷、烟酰胺核糖、苯酰基甘氨酸、3-羟基-2-氨基苯甲酸、缬氨酸、高肌肽;受治疗组干预后下降的生物标记物有2个(VIP>1,P<0.05),分别为溶血磷脂酰胆碱和谷氨酸。结论解毒化瘀颗粒干预途径可能通过调整氨基酸、核苷酸、脂肪酸、磷脂及活性肽代谢,使ALF大鼠的内环境趋于平衡,改善疾病状态,从而发挥其解毒化瘀的作用。Objective Based on the metabolomics research strategy, the changes of metabolites in the urine of acute liver failure(ALF) rats were studied to explore the possible mechanism of Jieduhuayu granules in treating ALF rats. Methods 18 rats were randomly divided into 3 groups, each group 6, normal group, model group, respectively(acute liver failure group) and treatment group(detoxification blood group), ALF model is set up, the liquid chromatography-mass spectrometry(LC-MS) of metabonomics method of rat urine samples for testing, combined with mass spectrometry and public information retrieval to detect metabolites identified, using principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) metabolites differences between groups.Results Normal group, model group, treatment group of metabolic profile have obvious difference, screening and identified with a significant difference between normal group and model group of 8. There were 6 biomarkers were called back after intervention in the treatment group as Xanthosine, Phenylacetylglycine, Nicotinamideriboside, 3-Hydroxytetradecanedioic acid, L-Valine, Homocarnosine and 2 biomarkers decreased as LysoPC(18:2(9Z,12Z)), MG(P-18:0e/0:0/0:0)(VIP > 1, P< 0. 05). Conclusion The intervention pathway of Jieduhuayu granules may regulate the metabolism of amino acid nucleotide fatty acid phospholipid and active peptide to balance the internal environment of ALF rats, improve the disease state, and play the role of Jieduhuayu.

关 键 词：急性肝衰竭 解毒化瘀颗粒 尿液 生物标记物 代谢组学 

分 类 号：R285.5[医药卫生—中药学]