基础医学与临床 ›› 2019, Vol. 39 ›› Issue (3): 337-342.

• 研究论文 • 上一篇    下一篇

液相色谱-质谱研究高尿酸血症大鼠血清代谢组学

石拓1,2,卢存龙2,李龙3,朱厚鑫1,2,周岩冰1   

  1. 1. 青岛大学附属医院
    2. 青岛大学医学部
    3. 威海市中心医院
  • 收稿日期:2018-07-18 修回日期:2018-11-28 出版日期:2019-03-05 发布日期:2019-03-05
  • 通讯作者: 周岩冰 E-mail:zhouyanbing998@aliyun.com
  • 基金资助:
    胰腺星状细胞与胰腺癌上皮间质转换的正向反馈机制研究及其在胰腺癌化疗耐药中的作用

Metabolomic research on hyperuricemia in rats using UPLC-MS/MS

  • Received:2018-07-18 Revised:2018-11-28 Online:2019-03-05 Published:2019-03-05

摘要: 目的 利用液相色谱-串联质谱技术,研究高尿酸血症大鼠整体代谢谱的改变,筛选与高尿酸血症相关的潜在生物标记物。方法 通过腺嘌呤和氧嗪酸钾灌胃3周,同时自由进食含10%酵母膏饲料方法建立高尿酸血症大鼠模型。采用基于超高效液相色谱-质谱(UPLC-MS/MS)的代谢组学方法,运用主成分分析(PCA)和偏最小二乘判别分析(PLS-DA)分析比较模型组与正常大鼠血清的代谢谱差异。结果 与对照组大鼠相比,在高尿酸模型组大鼠中发现并鉴定出14种潜在生物标记物,分别为尿酸、次黄嘌呤、尿囊素、肌酐、马尿酸、犬尿氨酸、色氨酸、硫酸吲哚酚、硫酸对甲酚、牛磺酸、棕榈酸、硬脂酸、LPC(17:0)和LPC(18:0)。提示,高尿酸血症影响大鼠嘌呤代谢、氨基酸代谢、胆汁酸代谢、脂肪酸代谢及菌群代谢。结论 本研究筛选出高尿酸模型大鼠血清中的14种差异代谢物,有助于解释高尿酸血症引起的代谢改变,可望为高尿酸血症的早期筛查、诊断和治疗提供帮助。

关键词: 高尿酸血症, 胰岛素抵抗, 代谢组学, 超高效液相色谱-质谱

Abstract: Objective To investigate the comprehensive serum metabolic profiles of hyperuricemia rats and to screen potential biomarkers associated with hyperuricemia by using liquid chromatography-tandem mass spectrometry. Methods Hyperuricemia rat model was established by consistent daily intragastric administration of of adenine and potassium oxazinate for 3 weeks, rats were fed with 10% yeast extract at the same time. The metabolomics method based on ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS), principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to compare the difference of serum metabolic profiles between hyperuricemia model and control groups. Results Comparing with control rats, 14 potential biomarkers were identified in hyperuricemia rats, such as uric acid, hypoxanthine, allantoin, creatinine, hippuric acid, kynurenine, tryptophan, indoxyl sulfate, p-cresol sulphate, taurine, palmitic acid, stearic acid, LPC (17:0) and LPC (18:0). The results showed that hyperuricemia affected purine metabolism, amino acid metabolism, bile acid metabolism, fatty acid metabolism and gut microbiota metabolism in rats. Conclusions In this study, 14 different serum metabolites of hyperuricemia model rats were screened, which were helpful to explain the metabolic profiles changes caused by hyperuricemia, and to provide help for early screening, diagnosis and treatment of hyperuricemia.

Key words: hyperuricemia, insulin resistance, metabolism, ultra-high performance liquid chromatography-mass spectrometry