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中国临床药理学与治疗学 ›› 2021, Vol. 26 ›› Issue (3): 292-298.doi: 10.12092/j.issn.1009-2501.2021.03.008

• 临床药理学 • 上一篇    下一篇

基于代谢组学研究对乙酰氨基酚片对中国健康成人胆汁酸谱的影响

杨倩1,俞蕴莉2,张全英2
  

  1. 1苏州大学,苏州 215004,江苏;2苏州大学附属第二医院临床药理实验室,苏州 215004,江苏
  • 收稿日期:2020-09-09 修回日期:2020-12-17 出版日期:2021-03-26 发布日期:2021-04-06
  • 通讯作者: 张全英,通信作者,女,主任药师,硕士生导师,主要从事临床药理学方面研究。 Tel: 0512-67783687 E-mail: sdfeyyq@163.com
  • 作者简介:杨倩,女,硕士研究生,研究方向:临床药理学。 E-mail: 18895339423@163.com
  • 基金资助:
    国家自然科学基金(81603181)

Metabolomics-based analysis of serum BAs in healthy Chinese adults taking acetaminophen

YANG Qian1, YU Yunli2, ZHANG Quanying2   

  1. 1 Soochow University, Suzhou 215004, Jiangsu, China; 2 Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China
  • Received:2020-09-09 Revised:2020-12-17 Online:2021-03-26 Published:2021-04-06

摘要: 目的:研究健康成人多次口服对乙酰氨基酚片后胆汁酸代谢的变化。方法:招募10名健康受试者,收集受试者口服对乙酰氨基酚前后的血清标本,分为给药前组(PD),第5次给药后组(FD)及第8次给药后组(ED),采用高效液相串联质谱(LC-MS/MS)的方法,定量检测血清胆汁酸谱,并结合代谢组学的主成分分析(PCA),正交偏最小二乘法判别分析(OPLS-DA),研究多次口服对乙酰氨基酚后健康成人胆汁酸代谢谱的变化,检测各组肝功能生化指标,观察在给药前后肝功能生化指标的变化。 结果:在给药前和给药后人血清的胆汁酸谱发生了变化,牛磺鹅去氧胆酸(TCDCA),甘氨胆酸(GCA),甘氨鹅脱氧胆酸(GCDCA),牛磺熊去氧胆酸(TUDCA)的浓度与给药前的基线相比显著升高(P<0.05),肝功能生化指标无明显的变化。采用代谢组学的方法筛选出的差异代谢物GCA,GCDCA为口服对乙酰氨基酚后胆汁酸改变最敏感的指标。结论:GCA和GCDCA或可作为对乙酰氨基酚致早期肝损伤的潜在生物标志物。

关键词: 对乙酰氨基酚, 胆汁酸, 代谢组学, 高效液相色谱-质谱

Abstract: AIM: To investigate the changes of bile acid metabolism in healthy adults after taking acetaminophen.  METHODS: Ten healthy subjects were enrolled and the serum samples of subjects before and after multiple administration of acetaminophen were collected. They were divided into pre-dose group (PD), fifth-dose gro-up (FD) and eighth-dose group (ED). A high performance liquid chromatography-tandem mass spectrometric method (HPLC-MS/MS) was used to quantify 15 target-edbile acid metabolites in human plasma, combined with principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA)to investigate the changes of bile acid metabolism profile in healthy adults after taking acetaminophen. And the biochemical indicators of each group were detected. RESULTS: There was a change in the bile acid spectrum of human serum after taking acetaminophen. Compared with group PD, the taurochenodeoxycholicacid (TCDCA), glycocholicacid (GCA), glycochenodeoxycholic acid (GCDCA) and tauroursodeoxycholic acid (TUDCA) levels were significantly increased (P<0.05). There was no obvious changes in biochemical indicators. GCA and GCDCA were the most sen-sitive indicators of bile acid. CONCLUSION: GCA and GCDCA can be used as potential biomarkers of early liver injury caused by acetaminophen.

Key words: acetaminophen, bile acid, metabolomics, LC-MS 

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