氨基酸代谢组学案例分析

氨基酸代谢组学案例分析

疾病研究：主动脉夹层分离病人血浆的氨基酸轮廓谱研究 

研究对象：人

分析检测平台：LC-MS/MS

期刊：Scientific Reports

影响因子：5.228

发表时间：2017

摘要：

Aortic dissection (AD), a severe cardiovascular disease with the characteristics of high mortality, is lack of specific clinical biomarkers. In order to facilitate the diagnosis of AD, we investigated plasma amino acid profile through metabolomics approach. Total 33 human subjects were enrolled in the study: 11 coronary heart disease (CHD) patients without aortic lesion and 11 acute AD and 11 chronic AD. Amino acids were identified in plasma using liquid chromatography and mass spectrometry (LC-MS/MS), and were further subjected to multiple logistic regression analysis. The score plots of principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) showed clear discrimination of CHD patients with AD, acute AD or chronic AD patients, respectively. The contents of histidine, glycine, serine, citrate, ornithine, hydroxyproline, proline and sarcosine were significant different in acute AD patients comparing with CHD patients. The levels of citrate, GABA, glutamate and cysteine were significant different in chronic AD patients comparing with CHD patients. The contents of glutamate and phenylalanine were significant changed in acute AD patients comparing with chronic AD patients. Plasma aminograms were significantly altered in patients with AD comparing with CHD, especially in acute AD, suggesting amino acid profile is expected to exploit a novel, non-invasive, objective diagnosis for AD.

Keywords: Aortic dissection (AD) ，liquid chromatography and mass spectrometry (LC-MS/MS) , plasma amino acids profile

研究背景：

主动脉夹层分离是一种潜在的高死亡率的血管疾病，其中主动脉腔内血液从主动脉内膜撕裂处进入主动脉中膜分离，沿主动脉长轴方向扩展形成主动脉壁的二层分离状态，该状态的主动脉容易扩大出现致死性大动脉破裂。如果没有及时治疗，48小时内的死亡率达到50%-60%而两个星期内的死亡率高达80%，因此及时性的诊断治疗就是拯救生命。

目前为止，主动脉夹层分离主要的诊断方法有螺旋计算机断层扫描血管造影、磁共振成像或术中可视化技术如经胸廓或食道的超声心动图。这些技术不仅价格昂贵，而且患者需要转移到特殊的诊断中心。此外，广泛使用的螺旋计算机断层扫描血管造影技术让患者暴露在海量的辐射下，可能会诱发速发型过敏反应和介质对比肾病。因此，发现能够预警主动脉夹层分离疾病的生物标记物，不但对帮助医生进行及时的诊断和治疗具有重大意义，而且能够拯救主动脉夹层分离患者宝贵的生命。

人体的20%是由氨基酸及其代谢物组成，在人体中各项代谢中具有重要的作用。已有报道表明肝硬化和非小肺细胞癌患者的血浆中氨基酸浓度具有显著性差异。此外，血浆的氨基酸轮廓谱能够被用于区分乳腺癌患者、食管癌患者、头颈癌患者与健康人群。因此，本文拟采用血浆的氨基酸轮廓谱技术研究主动脉夹层分离患者和冠心病患者的氨基酸表达差异，从而为主动脉夹层分离疾病的诊断和治疗提供新的方法和技术。