亚硒酸钠对大鼠代谢产物影响的核磁共振研究

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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。 In this paper, the use of nuclear magnetic resonance (1HNMR) technology to study the maximum tolerated intake conditions of sodium selenite on rat urine metabolites. The results showed that the peak signals of the metabolites of formic acid, acetic acid, lactic acid, alanine, succinic acid, glycine, hippuric acid, phenylalanine and tryptophan were significantly increased in the urine of rats, while citric acid, creatine , The peak signal of urea, urea and trimethylamine oxide (TAMO) decreased significantly. Lactic acid, citric acid and succinic acid are intermediate products of the tricarboxylic acid cycle in the body, and their metabolic abnormalities are the markers of energy metabolism disorders. The metabolic abnormalities of hippurate, phenylalanine and alanine, filtration and recovery of glomeruli Function; acetic acid and glycine metabolic abnormalities is a sign of liver damage, the results of tissue sections also proved that the rat liver and kidney damage have occurred, consistent with the results of 1HNMR. The level of 8 OHdG (8 hydroxyl 2 ’deoxyguansoine) in the urine was significantly increased after the addition of sodium selenite was detected by HPLC, which proves the occurrence of oxidative damage in vivo. The above results indicate that supplementation with sodium selenite at the highest tolerated intakes is unsafe and NMR methods are useful for elucidating the toxicological molecular basis of selenium.
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