张翠,台晶杰,崔文静,金艺,徐海燕,袁波
ZHANG Cui,TAI Jingjie,CUI Wenjing,JIN Yi,XU Haiyan,YUAN Bo

• 1:沈阳药科大学药学院

摘要(Abstract)：

目的基于代谢组学研究策略,研究大鼠尿液中内源性代谢物的变化,探寻与阿尔茨海默病(Alzheimer's disease,AD)相关的潜在生物标志物,为AD的临床诊断提供新的思路。方法大鼠双侧海马注射凝聚态β淀粉样蛋白1-42(Aβ1-42)建立AD模型,采用超高效液相色谱质谱联用(UPLCMS)技术对模型组和假手术组大鼠尿液代谢物谱进行分析测定,以OPLS(orthogonal partial least squares)方法对得到的数据进行统计学分析,研究2组之间内源性代谢产物的差异。结果经OPLS分析,2组大鼠尿液的代谢特征存在明显差异,发现了8个与AD相关的潜在生物标志物(含有2个未知化合物)。与假手术组相比,AD模型组大鼠尿液中苯丙氨酸、苯乙酰甘氨酸、N2-琥珀酰-L-鸟氨酸、高香草酸的含量明显升高(P<0.05,P<0.01),而肌酸酐、异戊酰丙氨酸含量则明显降低(P<0.01)。结论 AD模型组大鼠与假手术组大鼠在尿液代谢水平上具有明显差异,具有明显变化的代谢物(苯丙氨酸、苯乙酰甘氨酸、N2-琥珀酰-L-鸟氨酸、高香草酸、肌酸酐、异戊酰丙氨酸)有可能作为AD潜在的尿液生物标志物,为AD的早期临床诊断和治疗提供参考。
Objective To explore the difference of metabolites in rat urine and identify the potential biomarkers of Alzheimer's disease(AD) of rats based on the metabonomics strategies,which could provide the newideas for the clinical diagnosis of AD. Methods Aggregated Aβ1-42 peptide was unilaterally injected into the hippocampal region to establish AD rat's model. The urine samples were analyzed by UPLC-MS and the resulting data matrices were analyzed by multivariate statistical analysis(the orthogonal to partial least squares,OPLS) to find the urine differential metabolites between AD group and sham group. Results OPLS analysis showed that the metabolic profiling of urine samples between AD group and sham group were significantly different,and six potential biomarkers in correlation with AD were identified,besides,two unknown compounds were also found. Comparing with the sham group,the levels of phenylalanine,phenylacetylglycine,N2-succinyl-L-ornithine and isovalerylalanine in AD group were increased(P < 0. 05,P < 0. 01),while the concentrations of creatinine and homovanillic acid in AD group were decreased considerably(P < 0. 01). Conclusions There were significant differences in urine metabolites' spectra between AD group and sham group,and the compounds including phenylalanine,phenylacetylglycine,N2-succinyl-L-ornithine,creatinine,isovalerylalanine and homovanillic acid may be served as the potential biomarkers,which will be used to assist physicians in fast diagnosis and early treatment of AD.

关键词(KeyWords)： 阿尔茨海默病;代谢组学;生物标志物;大鼠尿液;超高效液相色谱质谱联用
Alzheimer's disease;metabonomics;biomarker;rat urine;UPLC-MS

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 张翠,台晶杰,崔文静,金艺,徐海燕,袁波
ZHANG Cui,TAI Jingjie,CUI Wenjing,JIN Yi,XU Haiyan,YUAN Bo

DOI: 10.14066/j.cnki.cn21-1349/r.2018.03.007

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