早期阿尔茨海默病小鼠尿液核磁共振氢谱代谢组学研究

doi:10.3785/j.issn.1008-9292.2018.12.12

浙江大学学报（医学版）

2018, Vol. 47

Issue (6): 636-642 DOI: 10.3785/j.issn.1008-9292.2018.12.12

原著

早期阿尔茨海默病小鼠尿液核磁共振氢谱代谢组学研究

郑涌泉¹(

),章晓茜²,陈久霞³,周琦³,高红昌^3,*(

)

1. 浙江大学医学院附属妇产科医院药剂科, 浙江杭州 310006
2. 浙江大学医学院附属第一医院药剂科, 浙江杭州 310003
3. 温州医科大学药学院, 浙江温州 325035

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

ZHENG Yongquan¹(

),ZHANG Xiaoqian²,CHEN Jiuxia³,ZHOU Qi³,GAO Hongchang^3,*(

)

1. Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
2. Department of Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
3. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China

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摘要：

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。

关键词： 阿尔茨海默病/诊断; 阿尔茨海默病/病理生理学; 尿; 能量代谢; 甲胺类/代谢; 磁共振波谱学; 早期诊断; 疾病模型, 动物

Abstract:

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.

Key words: Alzheimer disease/diagnosis Alzheimer Disease/physiopathology Urine Energy metabolism Methylamines/metabolism Magnetic resonance spectroscopy Early diagnosis Disease models, animal

收稿日期: 2018-08-30 出版日期: 2019-03-15

R749.1+6

通讯作者: 高红昌 E-mail: 5515058@zju.edu.cn;gaohc27@wmu.edu.cn

作者简介: 郑涌泉(1989-), 男, 硕士, 初级药师, 主要从事医药核磁共振代谢组学研究; E-mail:5515058@zju.edu.cn; https://orcid.org/0000-0002-6091-8265

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引用本文:

郑涌泉,章晓茜,陈久霞,周琦,高红昌. 早期阿尔茨海默病小鼠尿液核磁共振氢谱代谢组学研究[J]. 浙江大学学报（医学版）, 2018, 47(6): 636-642.

ZHENG Yongquan,ZHANG Xiaoqian,CHEN Jiuxia,ZHOU Qi,GAO Hongchang. Metabonomics studies of urine from APP/PS1 mice with early-stage Alzheimer's disease. J Zhejiang Univ (Med Sci), 2018, 47(6): 636-642.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2018.12.12 或 http://www.zjujournals.com/med/CN/Y2018/V47/I6/636

图 1 野生型小鼠和 APP/PS1 转基因小鼠尿液典型的核磁共振氢谱

图 2 野生型小鼠和 APP/PS1 小鼠尿液核磁共振氢谱的PLS-DA得分图和载荷图

表 1 野生型小鼠和 APP/PS1 小鼠尿液代谢物定量分析结果比较

图 3 阿尔茨海默病发病早期代谢差异示意图

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