摘要
目的结合血液生化分析和肾组织病理学检查,运用代谢组学方法研究纳米二氧化钛(TiO2)对大鼠肾功能的影响。方法雄性Wistar大鼠经静脉注射染毒0、1、5和15 mg/kg的纳米TiO2和15 mg/kg非纳米TiO2。连续染毒21d后,测定和检查大鼠的血浆生化指标和肾组织病理学改变,并分析尿液和血浆的1H-NMR代谢谱。结果与对照组相比,各纳米TiO2染毒组大鼠的尿素氮(BUN)和肌酐(CREA)水平明显升高。病理学检查显示,低中剂量组大鼠的肾小管上皮细胞发生肿胀,高剂量组大鼠的肾细胞出现点状坏死。尿液和血浆代谢组学研究结果表明,TiO2染毒组与对照组的代谢谱有明显差异,代谢成分乙酸和氧化三甲胺的水平发生变化。不同染毒剂量组动物的代谢谱各不相同,这些代谢谱图所提示的生理改变与肾脏病理和血浆生化改变相一致。结论纳米TiO2染毒后导致大鼠的肾功能发生损伤,并且代谢组学方法可用于纳米毒理学和安全性评价。
Objective The aim of this study was to evaluate the nephrotoxicity of nano-sized TiO2 by metabonomic approach. Methods Male Wistar rats were intravenously injected with nano-sized TiO2 particles at doses of 1, 5, 15 mg/kg body weight and micro-sized TiO2 particles at a dose of 15 mg/kg body weight. One group treated with vehicle was used as the control. The effects of particles on the renal function were studied after 21 days administration. Urine samples for 24 h were collected through the whole experiment every day and its 1H-NMR spectra were acquired, and subjected to data process and principal component analyses （PCA）. At end of the study, plasma was collected and its ~H-NMR spectra were acquired, and subjected to data process and Partial-Least- Squares Discriminant analysis （PLS-DA）. And all animals were taken blood biochemical analysis and liver histopathology examination. Results Twenty-one day treatment resulted in increases of blood urea nitrogen （BUN） and creatinine （CREA）. The histopathological examination showed tubular damages after treatment with nano-sized TiO2 particles. 1 H NMR spectroscopy analyses revealed the changes of acetic acid and trimethylamine oxide concentrations in urine and plasma. Conclusion The effect of nano-sized TiO2 on the rat urine and plasma metabonomic profile are related with nano-sized TiO2 nephrotoxicity, which support the contention that the metabonomic approach represents a promising new technology for the toxicology research of nano-sized particals.
出处
《毒理学杂志》
CAS
CSCD
北大核心
2009年第3期201-204,共4页
Journal of Toxicology
基金
国家973计划资助项目(2006CB705603)
关键词
纳米二氧化钛
肾毒性
代谢组学
核磁共振
模式识别
Nano-sized TiO2 particles
Nephrotoxicity
Metabonomies
Nuclear magnetic resonance
Pattern recognition
