Metabonomics study of urine and plasma in depression and excess fatigue rats by ultra fast liquid chromatography coupled with ion trap-time of flight mass spectrometry.
Metabonomics study of urine and plasma in depression and excess fatigue rats by ultra fast liquid chromatography coupled with ion trap-time of flight mass spectrometry.
复制标题
DOI：
10.1039/b914751a
复制
发表时间：
2010-05
影响因子：
--
通讯作者：
Fengxia Zhang;Z. Jia;P. Gao;Hongwei Kong;Xiang Li;Xin Lu;Yiling Wu;Guowang Xu
中科院分区：
文献类型：
--
作者：
Fengxia Zhang;Z. Jia;P. Gao;Hongwei Kong;Xiang Li;Xin Lu;Yiling Wu;Guowang Xu
采用快速液相色谱-离子阱-飞行时间质谱联用（UFLC/MS-IT-TOF）代谢组学方法研究抑郁和过度疲劳大鼠血浆和尿液的代谢变化。应用主成分分析（PCA）和偏最小二乘判别分析（PLS-DA）对抑郁、过度疲劳和对照组大鼠进行分类。选择对三组大鼠分类重要的代谢产物作为潜在的生物标志物，并通过UFLC/MS-IT-TOF分析获得的MS（n）信息进行鉴定。过度疲劳大鼠血浆精胺、丙酰肉毒碱、丁酰肉毒碱、苯丙氨酸、溶血磷脂酰胆碱（LPC）C14：0和LPC C18：2表达下调，甲基马尿酸和鹅去氧胆酸（CDCA）表达上调。抑郁症大鼠血浆精胺、亮氨酸、丙酰肉碱、丁酰肉碱显著降低，马尿酸、甲基马尿酸、胆酸、CDCA、LPC C16：0显著升高。抑郁和过度疲劳大鼠尿中N-乙酰基-L-精氨酸乙酯和N-甲基-2-吡啶酮-5-甲酰胺（2-PY）（或N-甲基-4-吡啶酮-3-甲酰胺（4-PY））的含量显著降低，亮氨酰脯氨酸和泛酸的含量显著升高。与对照组相比，抑郁症大鼠尿液中犬尿烯酸和N2-琥珀酰-L-鸟氨酸的浓度较低。抑郁和过度疲劳大鼠的相关网络显示抑郁大鼠的烟酸和烟酰胺代谢、精氨酸代谢、胆固醇代谢、色氨酸代谢和犬尿氨酸代谢异常，过度疲劳大鼠的能量代谢、烟酸和烟酰胺代谢和卵磷脂代谢异常。我们的研究结果为抑郁症和过度疲劳大鼠复杂的代谢机制提供了新的见解。
A novel metabonomic method based on fast liquid chromatography coupled with ion trap-time of flight mass spectrometry (UFLC/MS-IT-TOF) was applied to study the metabolic changes of plasma and urine in depression and excess fatigue rats. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied for classifying the depression, excess fatigue and the control rats. Metabolites which were important for the classification in the three groups of rats were selected as potential biomarkers and identified by MS(n) information achieved from UFLC/MS-IT-TOF analysis. Spermine, propionylcarnitine, butyrylcarnitine, phenylalanine, lysophosphatidylcholine (LPC) C14:0 and LPC C18:2 were down-regulated, methyl-hippuric acid and chenodeoxycholic acid (CDCA) were up-regulated significantly in plasma of the excess fatigue rats. Spermine, leucine, propionylcarnitine, and butyrylcarnitine decreased, hippuric acid, methyl-hippuric acid, cholic acid, CDCA and LPC C16:0 increased markedly in plasma of the depression rats. Ethyl N2-acetyl-L-argininate and N-methyl-2-pyridone-5-carboxamide (2-PY) (or N-methyl-4-pyridone-3-carboxamide (4-PY)) were down-regulated, leucylproline and pantothenic acid were up-regulated remarkably both in urine of depression and excess fatigue rats. The concentration of kynurenic acid and N2-succinyl-L-ornithine was low in urine of depression rats compared with control rats. Based on the data, correlation networks for depression and excess fatigue rats revealed the abnormality of nicotinate and nicotinamide metabolism, arginine metabolism, cholesterol metabolism, tryptophan metabolism and kynurenine metabolism in depression rats, and in excess fatigue rat alterations of energy metabolism, nicotinate and nicotinamide metabolism and lecithin metabolism. Our results provide novel insights in the complex metabolic mechanisms occurring in depression and excess fatigue rats.