基于LC-MS代谢组学的雷公藤多苷致肝毒性生物标志物的初步筛查

Investigation of metabolites of Triptergium wilfordii on liver toxicity by LC-MS

筛查雷公藤多苷片肝毒性产生的特征性生物标志物,并初步探讨其可能的作用机制,为雷公藤多苷片肝毒性提供可能的辅助检测指标和筛查诊断的方法。采用液相色谱-质谱方法测定空白组大鼠与口服雷公藤多苷片高剂量模型组大鼠代谢指纹谱,利用多元统计分析方法比较2组的代谢谱差异,筛选出可能的潜在生物标志物。实验共筛选出20个在模型组中与正常组中差异性较大的代谢物(VIP>1.0),分析鉴定了7个代谢物,分别为6-磷酸葡萄糖胺、溶血磷脂、色氨酸、胍基乙酸、3-吲哚丙酸、可的松和泛醌,其代谢水平的变化表明氨基酸代谢、糖代谢、磷脂代谢和激素代谢等途径发生紊乱。由此推测雷公藤多苷片致肝损伤可能与三羧酸循环中能量代谢和尿素循环中氨基酸代谢,以及糖代谢异常有关,该研究可为今后进一步研究雷公藤肝毒性提供一定的数据支持。

In this paper, biomarkers of liver toxicity of Triptergiurn wilfordii based on metabolomics was screened, and mechanism of liver toxicity was explored to provide a reference for the clinical diagnosis for liver toxicity of Triptergium wilfordii. MS method was cartied on the analysis to metabolic fingerprint spectrum between treatment group and control group. The potential biomarkers were compared and screened using the multivariate statistical methods. As well, metabolic pathway would be detailed description. Combined with PCA and OPLS-DA pattern recognition analysis, 20 metabolites were selected which showed large differences between model group and blank group （VIP 〉 1.0 ）. Seven possible endogenous biomarkers were analyzed and identified. They were 6-phosphate glucosamine, lysophospholipid, tryptophan, guanidine acetic acid, 3-indole propionic acid, cortisone, and ubiquinone. The level changes of above metabolites indicated that the metabolism pathways of amino acid, glucose, phospholipid and hormone were disordered. It is speculated that liver damage of T. wilfordii may be associated with the abnormal energy metabolism in citric acid cycle, amino acid metabolism in urea cycle, and glucose metabolism. It will be helpful to further research liver toxicity ingredients of Triptergium wilfordii.