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基于氢核磁共振波谱的代谢组学研究脑缺血/再灌注后大鼠脑脊液中的生物标志物

(1)H NMR-based metabolomics exploring biomarkers in rat cerebrospinal fluid after cerebral ischemia/reperfusion.

作者信息

Wang Yun, Wang Yigang, Li Mei, Xu Pengcheng, Gu Tao, Ma Tengfei, Gu Shuling

机构信息

Jiangsu Key Laboratory of Anaesthesia, XuZhou Medical College, XuZhou, JiangSu, China.

出版信息

Mol Biosyst. 2013 Mar;9(3):431-9. doi: 10.1039/c2mb25224d. Epub 2013 Jan 23.

DOI:10.1039/c2mb25224d
PMID:23340987
Abstract

In our study, metabolomics was used to investigate biochemical changes in the early stages of rats focal cerebral ischemia/reperfusion (I/R) injury. Cerebrospinal fluid (CSF) samples at 0, 0.5, 1, 3, and 6 h of reperfusion (n = 10), based on (1)H NMR spectroscopy and multivariate data analyses, were tested to analyze the changing of metabolites during the early disease process. Partial least squares-discriminant analysis scores plots of the (1)H NMR data revealed clear differences among the experiment groups. Combining the results of the loading plot and t-test, we found that twenty-seven metabolites were changed significantly (p < 0.05) in the CSF samples among the different groups. Among that, the potential biomarkers in CSF of ischemic rats were: acetic acid, 3-hydroxyisovaleric acid, 3-hydroxybutyric acid, choline, l-alanine, creatine, creatinine, glycine, pyruvic acid, glycerol, glutamic acid, d-fructose, l-lactic acid and acetone. These findings help us understand the biochemical metabolite changes in CSF of I/R rats in early stages. What's more, metabolomics may, therefore, have the potential to be developed into a clinically useful diagnostic tool of ischemic brain injury.

摘要

在我们的研究中,代谢组学被用于研究大鼠局灶性脑缺血/再灌注(I/R)损伤早期的生化变化。基于氢核磁共振波谱(1H NMR)和多变量数据分析,对再灌注0、0.5、1、3和6小时的脑脊液(CSF)样本(n = 10)进行检测,以分析疾病早期过程中代谢物的变化。1H NMR数据的偏最小二乘判别分析得分图显示实验组之间存在明显差异。结合载荷图和t检验的结果,我们发现不同组CSF样本中有27种代谢物发生了显著变化(p < 0.05)。其中,缺血大鼠CSF中的潜在生物标志物有:乙酸、3-羟基异戊酸、3-羟基丁酸、胆碱、L-丙氨酸、肌酸、肌酐、甘氨酸、丙酮酸、甘油、谷氨酸、D-果糖、L-乳酸和丙酮。这些发现有助于我们了解I/R大鼠早期CSF中的生化代谢物变化。此外,代谢组学因此可能有潜力发展成为一种临床上有用的缺血性脑损伤诊断工具。

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