基于GC-MS的溴鼠灵毒性代谢组学研究

GC-MS based metabonomics studies on urine of rats treated with brodifacoum

目的运用尿液代谢组学方法对溴鼠灵毒性进行研究,揭示溴鼠灵干预对大鼠毒性作用的分子机制。方法采用气相色谱-质谱建立大鼠尿液的代谢指纹谱,采用主成分分析和偏最小二乘法判别分析比较溴鼠灵给药前后的代谢谱差异,利用正交偏最小二乘判别分析法找出与溴鼠灵毒性作用相关的差异代谢物。结果 PLS-DA得分图显示大鼠不同时点尿液样本代谢物轨迹在各时间段内相似度较好,呈现各自聚类现象。溴鼠灵中毒后,可诱导DNA损伤和突变,机体对神经损伤、肾损伤也出现修复、保护性反应。结论该研究结果表明代谢组学可为溴鼠灵毒性作用机制研究提供技术支持。

Objective To investigate the toxicity of brodifacoum with urine metabonomics, helping to understand the molecular mechanism of brodifacoum toxicity. Methods The metabolic profiles of urine sample were obtained with gas chromatography-mass spectrometry(GC-MS). The data were further analysed with principal component analysis(PCA), partial least squares analysis-discrimination analysis(PLS-DA) and orthogonal partial least squares analysis-discrimination analysis(OPLS-DA). The important differential metabolites closely related to toxicity of brodifacoum were discovered based on VIP(variable importance in projection) value and student’s test. Results PLS-DA score plot showed that the urinary metabolic profiles at different time points had good similarity within the time period and presented clustering phenomenon. The results revealed that brodifacoum caused DNA damages and mutations, and the organism showed repairing and protective response on nerve damages and kidney damages. Conclusion These results suggested that metabonomics technology provided a novel tool for the study on mechanism of brodifacoum toxicity.