壬基酚和辛基酚联合染毒的尿液代谢组学研究

运用代谢组学方法研究壬基酚和辛基酚联合染毒对大鼠尿液代谢的影响.在高效液相色谱-飞行时间质谱技术检测的基础上,通过主成分分析观察了联合染毒的时间-毒效应和剂量-毒效应.根据主成分分析和判别分析,结合t检验,筛选出染毒组和对照组中具有明显差异的化合物,并在Metlin Scripps Center for Mass Spectrometry代谢物数据库中查询,推断其可能的代谢标志物.结果表明,壬基酚和辛基酚联合染毒后,尿液中可能出现的生物标志物有5种,分别为4,8-二羟基喹啉-2-甲酸(黄尿酸)、色氨酸及N-乙酰-5-羟色胺、RG- 13022和十六碳烯酸.由这些物质涉及的代谢途径,推测壬基酚和辛基酚联合染毒可能对生物体的蛋白质代谢、神经系统和心血管系统、生物节律、细胞抗氧化、性激素的平衡等方面产生毒效应,另外还可能影响细胞的信号传递和脂类代谢.

Study on Urine Metabonomics of Joint Exposure to Nonylphenol and Ocytlphenol

Metabonomics approach was applied to investigate the effects of joint exposure to nonylphenol(NP) and ocytlphenol(OP) in sprague dawley rat.The metabolites in urine samples were detected by high performance liquid chromatography coupled with time-of-flight mass spectrometry(HPLC/QTOF-MS).Time-response and dose-response toxicity were observed based on the principle components analysis(PCA).Meanwhile,the potential biomarkers were screened out according to PCA,discriminant analysis(DA) and t-test,and identified with the Metlin Scripps Center for mass spectrometry metabolite database.The results indicated that the contents of xanthurenic acid,tryptophan,N-acetylserotonin,RG-13022 and hexadecenoic acid changed significantly in urine after exposure to NP and OP,which might be latent biomarkers.Joint exposure of NP and OP might produce toxic effects on protein metabolism,nervous system,cardiovascular system,biorhythm,cell anti-oxidant activity and balance of sex hormone.In addition,their toxicity might involve cellular signal transduction and lipometabolism.This study not only revealed the toxicity characteristics of combined exposure to NP and OP,but also provided references for further study on toxic mechanism of Alkylphenol.