基于GC-MS研究百草枯中毒模型小鼠血清代谢产物变化

Study on serum metabolism in mouse with PQ toxicity based on GC-MS techinique

目的基于气相色谱-质谱联用技术(G C-M S)分析百草枯中毒模型小鼠血清代谢谱的变化,研宂其代谢组学特征及其密切相关的代谢产物,探讨其分子机制及特征代谢物的潜在临床价值。方法灌胃30m g/kg百草枯建立百草枯中毒小鼠模型,应用G C-M S技术对血清样本进行检测,对检测结果应用主成分分析、正交偏最小二乘法-判别分析进行模式识别,然后通过变量重要性因子、/检验,结合数据库检索筛选出具有显著差异的代谢物。结果与对照组相比,模型组血清中的肌酐、脯氨酸、柠檬酸、琥珀酸、牛磺酸、苏糖酸、富马酸、甘氨酸、磷酸甲酯含量增加(P<0.05),而软脂酸、生育酚、色氨酸和6-磷酸葡糖酸含量减少(P<0.05)。结论通过对百草枯中毒模型小鼠血清代谢组学分析,证明代谢组学方法用于百草枯中毒研究是可行的,找到了与百草枯中毒密切相关的代谢信息,有助于阐明百草枯中毒机制。

O bjective To analyze the changes in plasma metabolism-using gas chromatography-mass spectrometry(GC-MS) of PQ toxicity in mouse, study its characteristics of metabolism and the metabolites that closely related toPQ toxicity, and assess the potential clinical value o f its molecular mechanism and characteristic metabolites. MethodsAnimal model of PQ toxicity was created using administration by gavage of 30mg/kg PQ. After the models were built,serum samples of five mice in the model group and five in the control group were detected applying GC-MS, the resultswas analyzed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLSDA).Several metabolites which were different between the two groups based on variable importance in projection (VIP)value, student's test and screening in databases were identified. Results Compared with the control group, the serumlevels of creatine, proline, citric acid, succinic acid, taurine, threonic acid, fumaric acid, glycine and methyl phosphatein the model group increased (/?<0.05) and palmitoleic acid, alpha-Tocopherol, cystine and 6-phosphogluconic aciddecreased (p<0.05). Conclusion Through serum metabonomics analysis of PQ toxicity in mouse demonstrates that themethod of metabonimics is feasible for the study of PQ toxicity, which highly-related metabolic information is found. Thefinding is helpful to understand the molecular mechanism of the PQ toxicity and provide a new direction for its clinicaldiagnosis and treatment.