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

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

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。

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.