The metabonomics of aging and development in the rat:: an investigation into the effect of age on the profile of endogenous metabolites in the urine of male rats using 1H NMR and HPLC-TOF MS
The metabonomics of aging and development in the rat:: an investigation into the effect of age on the profile of endogenous metabolites in the urine of male rats using 1H NMR and HPLC-TOF MS
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DOI：
10.1039/b500852b
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发表时间：
2005-07-01
影响因子：
--
通讯作者：
Wilson, ID
中科院分区：
文献类型：
--
作者：
Williams, RE;Lenz, EM;Wilson, ID
使用H-1 NMR光谱和HPLC-TOF MS（采用电喷雾电离（ESI））研究了雄性Wistar大鼠的衰老和发育对尿液中排泄的内源性代谢物谱的影响。从4周龄刚断奶后至20周龄，每两周从雄性大鼠中采集一次样品，分析内源性代谢物。多变量数据分析使数据中的集群能够根据年龄可视化，两种分析技术在4周和6周收集的尿液显示出最大差异。通过H-1 NMR光谱检测的标记物包括肌酐、牛磺酸、马尿酸盐和与氨基酸/脂肪酸相关的共振，其随年龄增加，而柠檬酸盐和葡萄糖/肌醇产生的共振下降。通过HPLC-MS检测到许多离子，这些离子仅存在于4周龄时的尿液样品中，在正ESI和负ESI中，离子范围（包括例如肉毒碱）随年龄增加。通过PLS回归建模进行的年龄预测表明，在这些数据中存在年龄相关趋势，HPLC-MS为4 - 12周，NMR为4 - 16周。这些技术的代谢组学研究的年龄相关的变化在大鼠的可能效用进行了讨论，并强调了采用合适的控制动物在药理学和毒理学研究的重要性。
The effect of aging and development in male Wistar-derived rats on the profile of endogenous metabolites excreted in the urine was investigated using both H-1 NMR spectroscopy and HPLC-TOF MS using electrospray ionisation (ESI). The endogenous metabolites were profiled in samples collected from male rats every two weeks from just after weaning at 4 weeks up to 20 weeks of age. Multivariate data analysis enabled clusters to be visualised within the data according to age, with urine collected at 4 and 6 weeks showing the greatest differences by both analytical techniques. Markers detected by H-1 NMR spectroscopy included creatinine, taurine, hippurate and resonances associated with amino acids/fatty acids, which increased with age, whilst citrate and resonances resulting from glucose/myomositol declined. A number of ions were detected by HPLC-MS that were only present in urine samples at 4 weeks of age in both positive and negative ESI, with a range of ions, including e.g. carnitine, increasing with age. Age predictions by PLS-regression modelling demonstrated an age-related trend within these data, between 4 and 12 weeks for HPLC-MS and 4-16 weeks for NMR. The possible utility of these techniques for metabonomic investigations of age-related changes in the rat is discussed and the importance of employing suitable control animals in pharmacological and toxicological studies is highlighted.