硫酸氧钒毒性的核磁共振代谢组学方法研究  

Toxicity Study of VOSO_4 Using NMR-based Metabonomics

作　　者：董继扬[1] 危阳洋[1,2] 戴晓侠[2] 邓伶莉[1] 陈忠[1,2] 

机构地区：[1]厦门大学物理系固体表面物理化学国家重点实验室,厦门361005 [2]厦门大学生物材料系,厦门361005

出　　处：《化学学报》2010年第17期1758-1764,共7页Acta Chimica Sinica

基　　金：卫生部科学研究基金-福建省卫生教育联合攻关计划(No.WKJ2008-2-36);福建省自然科学基金(No.2009J01299)资助项目

摘　　要：采用基于核磁共振(NMR)的代谢组学方法,结合生化指标分析及组织病理学检测,研究了具有类胰岛素活性的硫酸氧钒(VOSO4)对Wistar大鼠的毒性作用.通过不同剂量的VOSO4对Wistar大鼠连续灌胃给药16d,收集大鼠的血清和尿液,并采集样品的1H NMR谱进行多变量数据统计分析来辨识其特征代谢物,然后采用TICL(a web Tool for automatic Interpretation of Compound List)方法建立特征代谢物的代谢网络模型,分析受影响的主要代谢途径及其相互关系.研究结果表明:高剂量组(45mg/kg)和低剂量组(15mg/kg)的特征代谢物含量与对照组存在明显的差异;与对照组相比,高剂量和低剂量组血清中乳酸、肌氨酸酐以及牛磺酸等代谢物的含量增加,尿液中氧化三甲胺(TMAO)、肌酐、牛磺酸和甘氨酸等代谢物的含量增加,并呈现显著的剂量依赖关系;给药组中乙酸和琥珀酸的含量都降低.这些结果说明VOSO4可能影响大鼠体内的糖代谢、脂类代谢及肠道菌群代谢等多个代谢系统,高剂量的VOSO4会导致肝脏毒性和肾脏损伤.NMR-Based metabonomics combined with clinical biochemical analysis and histopathological examination was applied to investigate the toxicity effects of vanadyl sulfate with insulin-like activity in male Wistar rats. Male Wistar rats were administrated with VOSO4 at doses of 15 and 45 mg/kg body weight by intragastric administration for 16 d. Urine and serum samples were collected and analyzed by 1H NMR experiment. Multivariate analyses were employed to identify the characteristic metabolites for the toxicity effects of vanadyl sulfate. Then the metabolic networks of these characteristic metabolites were built up using TICL （a web Tool for automatic Interpretation of Compound List）. The relationship between the characteristic metabolites and the main matebolic pathways perturbed were analyzed and discussed. The differences of metabolic profiles were examined among high-dose （45 mg/kg）,low-dose （15 mg/kg） of VOSO4 and control groups. Compared to the control group,increased levels of lactate,creatinine and taurine in serum and increased excretion of trymethylamine-N2-oxide,creatinine,taurine and glycine in urine were found in both high-and low-dose groups which showed an obvious dose-dependent relationship. On the other hand,the concentration of acetate and succinate were decreased in both serum and urine samples of dosed groups. These results indicate that VOSO4 have disturbed the carbohydrate metabolism,lipid metabolism and gut microflora and the high-dosage of VOSO4 may cause liver and kidney injury.

关 键 词：核磁共振(NMR) 代谢组学 毒性 硫酸氧钒 化合物集合自动解释网络工具(TICL) 

分 类 号：R99[医药卫生—毒理学]