早期阿尔茨海默病小鼠尿液核磁共振氢谱代谢组学研究

目的: 基于核磁共振代谢组学方法探索阿尔茨海默病（AD）模型APP/PS1小鼠发病早期（4月龄）尿液中代谢物的变化。方法: 通过代谢笼收集16周龄APP/PS1小鼠（n=13）和野生型小鼠（n=15）的尿液，利用一维NOESY脉冲序列采集核磁共振氢谱，积分数据导入SIMCA-P+12.0软件进行模式识别分析，从而在整体代谢水平上探索AD发病早期尿液中代谢物的变化。结果: 与野生型小鼠比较，APP/PS1小鼠尿液的代谢轮廓明显不同，能量代谢、甲胺代谢、氨基酸代谢等代谢产物出现变化，其中3-羟基丁酸、2-羟基丁酸、琥珀酸、2-酮戊二酸、柠檬酸、顺乌头酸和延胡索酸的水平降低，乙酸、三甲胺、牛磺酸、肌酐、马尿酸、甲酸、葫芦巴碱、尿素的水平升高，差异均有统计学意义（均P < 0.05）。结论: AD发病早期小鼠能量代谢、甲胺代谢等途径已发生紊乱，这一结论有助于进一步认识AD的发病机制并为临床诊断提供新的思路。

Metabonomics studies of urine from APP/PS1 mice with early-stage Alzheimer's disease

Objective: To investigate the metabolic profiles of urine from APP/PS1 mice with early-stage Alzheimer's disease (AD). Methods: Urine samples were collected from 13 APP/PS1 mice of 16 weeks and 15 wild-type mice. ¹H-NMR spectroscopy was acquired with a one-dimensional NOESY pulse sequence, and the integral values were imported to SIMCA-P+12.0 software for analysis. Results: The metabonomic analysis showed that the metabolic profiles of the APP/PS1 mice were significantly different from that of age-matched wild-type mice. The levels of 3-hydroxybutyrate, 2-hydroxybutyrate, succinic acid, 2-ketoglutaric acid, citric acid, cis-aconitic acid, fumaric acid decreased, and those of acetic acid, trimethylamine, taurine, creatinine, hippuric acid, formic acid, trigonelline, urea increased (all P < 0.05). Conclusion: Metabolic pathways including glucose metabolism and methylamine metabolism may be involved in the pathogenesis of early AD.