【摘要】 目的:通过代谢组学技术考察栀子对大鼠内源性代谢物的影响,探讨其毒性代谢途径和可能机制。方法:以栀子为示例药物,以大鼠为研究对象,分为正常组和栀子组(给药组,灌胃栀子溶液),连续给予21 d。采集大鼠血清样本进行UPLC-MS检测,用主成分分析(PCA)结合正交偏最小二乘判别分析(OPLS-DA)进行代谢差异表征,寻找差异代谢物及可能的代谢通路。结果:代谢组学分析显示,组间代谢差异明显,与正常组比较,栀子组血清样本中分别鉴定出11个差异代谢物,这些代谢物水平存在明显的变化。结论:栀子对肝、肾脏具有一定的毒性;栀子产生肝肾毒性的机制可能与葡萄糖、尿苷、肌苷、溶血磷脂酰胆碱(LPC16:0、LPC18:2)下降有关。栀子组sn-甘油基-3-胆碱磷酸明显上升,D-谷氨酰胺、葡萄糖、尿苷、肌苷、十八碳烯酸、紫胶桐酸、十二碳六烯酸、LPC 16:0、LPC 18:2、l-α-磷脂酰乙醇胺(大豆)明显下降。更多还原

【Abstract】 Objective:The effect of Fuetus toosendan on endogenous metabolites of rats were analyzed by means of metabolomics, and the metabolic pathway and possible mechanism of it toxicity were discussed. Methods: Use Fuetus toosendan as an example drug, rats as the research objects, except for the normal group, each administration group was given corresponding solution continuous administration for 21 days.The serum,liver and kidney samples of rats were detected by UPLC-MS and characterized by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA)to identify the potential biomarkers and possible metabolic pathways. Results:Metabolomics analysis showed that there were significant differences in metabolism among the groups. Compared with the normal group, 11 different metabolites were identified in serum samples of Gardenia jasminoides group, and the levels of these metabolites were significantly changed.Conclusion: Gardenia fruit has certain toxicity to liver and kidney. The mechanism of hepatorenal toxicity in Gardenia jasminoides may be related to the decrease of glucose, uridine, inosine and lysophosphatidylcholine(LPC16:0, LPC18:2). In gardenia group, Sn-glyceryl-3-choline phosphoric acid was significantly increased, while D-glutamine, glucose, uridine,inosine, octadecenoic acid, lalac acid, dodecahexaenoic acid, LPC 16:0, LPC 18:2 and L-α-phosphatidylethanolamine(soybean) were significantly decreased.更多还原