三聚氰胺污染饲料致大鼠肾毒性的代谢组学研究  

Nephrotoxic effect of melamine-contaminated fodder on rat:a metabonomic study

作　　者：窦春艳[1,2] 郑兴宇[1,2] 秦雪梅[1] 李震宇[1] 薛水玉[1,2] 高晓霞[1] 

机构地区：[1]山西大学中医药现代研究中心 [2]山西大学化学化工学院,山西太原030006

出　　处：《中国药理学与毒理学杂志》2011年第1期88-92,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目(30772759)~~

摘　　要：目的探讨三聚氰胺污染饲料致大鼠尿液和肾脏组织内源性代谢产物的变化,寻找三聚氰胺污染饲料致大鼠肾毒性的差异代谢物。方法大鼠喂食三聚氰胺污染饲料20 d后,通过光学显微镜观察大鼠肾脏组织病理变化,并采用气相色谱-质谱联用(GC-MS)分析手段对正常对照组和三聚氰胺组大鼠尿液和肾脏组织的代谢物进行分析。利用代谢组学分析软件SIMCA-P+11对大鼠尿液和肾脏组织采集的GC-MS数据进行多元统计分析。结果与正常对照组相比,三聚氰胺组大鼠肾脏组织部分纤维化,有大量尿酸盐结晶,可见颗粒管形病变。正常对照组和三聚氰胺组大鼠尿液和肾脏组织样品在主成分分析(PCA)中得到了很好的分离,并通过偏最小二乘判别分析(PLS-DA)指认引起差异的特征代谢物。与正常对照组相比,三聚氰胺组大鼠肾脏组织中丙氨酸显著上升;缬氨酸和乙醇胺等明显下降;尿液中乳酸显著上升,而半胱氨酸和尿嘧啶等明显下降。结论三聚氰胺污染饲料引起大鼠明显的肾毒性,尿液中有17种物质,肾脏组织中有11种物质被判定为可能特征代谢物。OBJECTIVE To explore the changes of endogenous metabolites in urine and kidney tissues of rats fed with melamine-contaminated fodder,and to find the biomarkers of nephrotoxicity.METHODS After rats in melamine group were given melamine-contaminated fodder for 20 d,pathological changes in kidneys were observed.Gas chromatography-mass spectrometry（GC-MS） was used to analyze the samples of urine and kidney tissues of rats in normal control and melamine groups.GC-MS data were analyzed by multivariate analysis with SIMCA-P ＋11 software.RESULTS Compared with normal control group,the fibrosis was seen in kidneys of rats in melamine group,accompanied by infiltration,a large ammount of urate crystal,and tube-type protein.Urine and kidney tissue samples in normal control and melamine groups were well separated by principal component analysis（PCA）,and the biomarker was found and identified by partial least squares-discrimination analysis（PLS-DA）.Compared with normal control group,alamine increased while valine and ethanolamine decreased in kidneys in melamine group,however,lactic acid increased significantly but cysteine and uracil decreased in urine.CONCLUSION Melamine can apparently induce toxicity on rat kindeys.Seventeen compounds in urine and eleven compounds in kindeys are regarded as possible biomarkers.

关 键 词：三聚氰胺 肾 毒性作用 代谢组学 气相色谱质谱法 

分 类 号：R994.4[医药卫生—毒理学] R969.1[医药卫生—药学]