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基于气相色谱-质谱联用技术的代谢组学鉴定出急性缺血性中风的氨基酸特征。

GC-MS-based metabolomics identifies an amino acid signature of acute ischemic stroke.

作者信息

Wang Dian, Kong Jing, Wu Jiayan, Wang Xingxing, Lai Minchao

机构信息

Department of Forensic Medicine, Shantou University Medical College, China.

Department of Neurology, First Affiliated Hospital of Shantou University Medical College, China.

出版信息

Neurosci Lett. 2017 Mar 6;642:7-13. doi: 10.1016/j.neulet.2017.01.039. Epub 2017 Jan 19.

Abstract

Ischemic stroke is a serious public health problem worldwide. Here, we characterized the metabolite features of acute ischemic stroke (AIS) using a gas chromatography-mass spectrometry-based metabolomics. Forty AIS patients and 29 sex and age-matched controls were recruited. The serum metabolic profiles were significantly different between the two groups. Compared to the controls, the patients had elevated levels of lactate, carbonate and glutamate (P<0.01), and lowered levels of alanine, citrate, glycine, isoleucine, leucine, serine, tyrosine, methionine, tryptophan, erythronic acid, urea, purine, hypoxanthine, and proline in the serum (P<0.05). Amino acids are the most important disturbed metabolites. Most dysregulated metabolites are closely correlated with each other and with several biochemical indices. The differential metabolites reflect pathophysiological processes of inflammation, energy deficit, oxidative stress, neurotoxicity, neuro excitation and injury. Tyrosine, lactate, and tryptophan were screened as a panel of potential biomarkers of AIS, jointly enabling a high precision (91.7%) to diagnose AIS by classification and regression tree (CRT). Collectively, we discovered a marked perturbation of metabolome of AIS in the serum, mainly associated with amino acid-related metabolism. Tyrosine, lactate, and tryptophan may be considered as potential biomarkers of AIS.

摘要

缺血性中风是全球范围内严重的公共卫生问题。在此,我们使用基于气相色谱 - 质谱联用的代谢组学方法对急性缺血性中风(AIS)的代谢物特征进行了表征。招募了40例AIS患者和29例年龄及性别匹配的对照。两组之间的血清代谢谱存在显著差异。与对照组相比,患者血清中乳酸、碳酸盐和谷氨酸水平升高(P<0.01),而丙氨酸、柠檬酸、甘氨酸、异亮氨酸、亮氨酸、丝氨酸、酪氨酸、蛋氨酸、色氨酸、赤藓糖酸、尿素、嘌呤、次黄嘌呤和脯氨酸水平降低(P<0.05)。氨基酸是受干扰最严重的代谢物。大多数失调的代谢物彼此之间以及与几个生化指标密切相关。差异代谢物反映了炎症、能量缺乏、氧化应激、神经毒性、神经兴奋和损伤的病理生理过程。酪氨酸、乳酸和色氨酸被筛选为AIS的一组潜在生物标志物,通过分类与回归树(CRT)联合诊断AIS的精度高达91.7%。总体而言,我们发现血清中AIS的代谢组存在明显扰动,主要与氨基酸相关代谢有关。酪氨酸、乳酸和色氨酸可被视为AIS的潜在生物标志物。

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