模型毒物急性毒性尿液核磁共振氢谱标记物的二阶段聚类分析  

Studies on the Acute Toxicity of Model Toxins by Proton Magnetic Resonance Spectroscopy of Urine Combined with Two-step Cluster Analysis

作　　者：吴惠丰[1] 张晓宇[1] 李晓晶[1] 廖沛球[1] 李伟生[1] 李中峰[1] 吴亦洁[1] 裴奉奎[1] 

机构地区：[1]中国科学院长春应用化学研究所,长春130022

出　　处：《分析化学》2006年第1期21-25,共5页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金资助项目(No.20575065)

摘　　要：采用现代核磁共振技术,通过分析给药肝、肾损伤模型化合物异硫氰酸α-萘酯(灌胃150 mg/kg体重)和二溴乙胺氢溴酸盐(腹腔注射250 mg/kg体重)24 h内W istar大鼠尿液的1H NMR谱,由尿液中内源性代谢物浓度变化研究了肝、肾模型毒物在大鼠体内的急性毒性。首次利用模式识别技术中的二阶段聚类分析方法解析大鼠尿液1H NMR谱确定了模型化合物尿液1H NMR标记物。结果表明,应用核磁共振和二阶段聚类分析相结合的方法,可提供模型化合物毒性比较清楚的认识。该方法也可用于金属化合物、中药及其它药物的毒性分类和预测研究以及建议各类靶向毒性的NMR标记物。^1H nuclear magnetic resonance （NMR） spectroscopy and two-step cluster analysis have been used to investigate the acute toxicity of model toxins. Male Wistar rats were treated with following model toxins, α-naphthyl isothioyanate （ANIT） and 2-bromoethanamine hydrobromide （BEA）. Urine samples from the rats dosed with these two compounds were collected over a course of 24 h and analyzed at 600 MHz ^1H NMR spectra. Each NMR spectrum was dataprocessed to provide 148 intensity-related descriptors of spectra. Urinary spectral data were analyzed by two-step cluster analysis （TSCA） methods and successful classification of the toxicities of model toxins was achieved. The NMR markers of various toxicities induced by model toxins were also clearly provided by TSCA. The combination of NMR and TSCA can be applied to the detection for the NMR markers of novel toxicities and prediction for the toxicities of other compounds.

关 键 词：尿液 核磁共振 毒性 模式识别 二阶段聚类分析 

分 类 号：R99[医药卫生—毒理学]