雷公藤多苷诱导肝损伤大鼠的血清溶血磷脂酰胆碱代谢轮廓

Metabolic profile of serum lysophosphatidylcholine in rats with liver injuryinduced by Tripterygium wilfordii multiglucoside

目的 研究雷公藤多苷(tripterygium wilfordii multiglucoside, TWM)诱导肝损伤大鼠的血清溶血磷脂酰胆碱(lysophosphatidylcholine, LPC)代谢轮廓。方法 采用UPLC-Q-TOF/MS技术定量分析空白组、TWM组和雷公藤甲素(triptolide, TP)组大鼠血清中15种LPCs,结合化学计量学方法分析大鼠灌胃TMW或TP后血清中LPC代谢轮廓的变化。结果 定量分析结果显示,TWM组11种LPCs、TP组13种LPCs的血清水平与空白组比较明显降低。主成分分析(principal component analysis, PCA)表明,TWM组和TP组大鼠血清LPC代谢轮廓均明显偏离空白组,且TP组偏离程度大于TWM组。正交偏最小二乘法-判别分析(orthogonal partial least squares-discriminant analysis, OPLS-DA)表明,LPC (14∶0)、LPC (20∶4)、LPC (18∶0)、LPC (18∶1)、LPC (17∶0)、LPC(22∶5)、LPC (16∶0)和LPC(17∶1)对OPLS-DA模型具有重要贡献,这8种LPCs血清水平与天冬氨酸转氨酶和丙氨酸转氨酶具有良好相关性(r>0.5,P<0.05),被鉴定为雷公藤多苷肝毒性的潜在生物标志。结论 血清LPC代谢轮廓与TWM和TP诱导的大鼠肝损伤密切相关。

Objective To investigate the metabolic profile of serum lysophosphatidylcholine(LPC)in rats with liver injury induced by tripterygium wilfordii multiglucoside(TWM).Methods The UPLC⁃Q⁃TOF/MS method was used to simultaneously quantify 15 LPCs in the serum of control,TWM-and triptolide(TP)-treated rats.Furthermore,chemometric analysis was applied to analyze the changes in the metabolic profiles of LPC in the serum of TWM-or TP⁃induced liver injured rats.Results The result of quantitative analysis showed that the serum levels of 11 LPCs in TWM group and 13 LPCs in TP group were significantly down⁃regulated when compared with control group.Principal component analysis(PCA)indicated that the serum LPC metabolic profiles of the two toxic groups were obviously different from the control group,and the deviation degree in TP⁃induced rats was greater than that in TWM⁃induced rats.Orthogonal partial least squares⁃discriminant analysis(OPLS⁃DA)showed that LPC(14∶0),LPC(20∶4),LPC(18∶0),LPC(18∶1),LPC(17∶0),LPC(22∶5),LPC(16∶0)and LPC(17∶1)had significant contributions on the OPLS⁃DA model,and the serum levels of the 8 LPCs were well related to the activities of biochemical indicators such as ALT and AST(r>0.5,P<0.05).Consequently,these LPCs were identified as potential biomarkers of hepatotoxicity of TWM-and TP⁃induced liver injury.Conclusion The metabolic profile of LPC is related closely to TWMand TP⁃induced liver injuries.