亚硒酸钠对大鼠代谢产物影响的核磁共振研究

Effect of Selenite at UL on the Metabolites in Rat Urine by ()~1H NMR Spectroscopy

本文采用核磁共振(1HNMR)技术研究了在最高耐受摄入量条件下补充亚硒酸钠对大鼠尿液代谢产物的影响。结果表明,在大鼠尿液中甲酸、乙酸、乳酸、丙氨酸、琥珀酸、甘氨酸、马尿酸、苯丙氨酸、色氨酸等代谢物谱峰信号显著增强,而柠檬酸、肌酸、尿素、尿甘素和氧化三甲胺(TAMO)的谱峰信号则显著降低。乳酸、柠檬酸和琥珀酸是体内三羧酸循环的中间产物,其代谢异常是能量代谢紊乱的标志;马尿酸、苯丙氨酸、丙氨酸的代谢异常与肾小球的滤过和回收功能有关;乙酸和甘氨酸的代谢异常则是肝功能损伤的标志,组织切片的结果也证明大鼠的肝和肾已经发生损伤,与1HNMR的结果相一致。采用HPLC检测到补充亚硒酸钠后尿液中8 OHdG(8 hydroxyl 2′ deoxyguansoine)水平显著升高,证明体内氧化损伤的发生。以上结果表明,在最高耐受摄入量条件下补充亚硒酸钠是不安全的,用NMR方法对阐明硒的毒理学分子基础是有效的。

The effects of selenium (Tolerable Upper Intake Level, UL) on the metabolism of rats have been investigated using (~1H NMR) spectra of urine. It showed that a range of low molecular weight compounds in urine were correlated with the severity of the selenium-induced liver and renal lesions. Urinary excretion, such as formate, lactate, acetate, hippurate, succinate, and alanine was increased following selenium treatment, whereas citrate, creatine, allantoin and TMAO excretion was decreased. The new founding was the appearance of formate in urine, which is correlated to free radicals. The results indicate that (~1H NMR) spectroscopy can be used to elucidate the toxicology of selenium at molecular level and it is useful for deciding the dose of selenium supplementation at UL.