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溃疡性结肠炎的代谢组学:诊断、生物标志物鉴定及病理生理学见解。

Metabonomics in ulcerative colitis: diagnostics, biomarker identification, and insight into the pathophysiology.

机构信息

Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Denmark.

出版信息

J Proteome Res. 2010 Feb 5;9(2):954-62. doi: 10.1021/pr9008223.

Abstract

Nuclear magnetic resonance (NMR) spectroscopy and appropriate multivariate statistical analyses have been employed on mucosal colonic biopsies, colonocytes, lymphocytes, and urine from patients with ulcerative colitis (UC) and controls in order to explore the diagnostic possibilities, define new potential biomarkers, and generate a better understanding of the pathophysiology. Samples were collected from patients with active UC (n = 41), quiescent UC (n = 33), and from controls (n = 25) and analyzed by NMR spectroscopy. Data analysis was carried out by principal component analysis and orthogonal-projection to latent structure-discriminant analysis using the SIMCA P+11 software package (Umetrics, Umea, Sweden) and Matlab environment. Significant differences between controls and active UC were discovered in the metabolic profiles of biopsies and colonocytes. In the biopsies from patients with active UC higher levels of antioxidants and of a range of amino acids, but lower levels of lipid, glycerophosphocholine (GPC), myo-inositol, and betaine were found, whereas the colonocytes only displayed low levels of GPC, myo-inositol and choline. Interestingly, 20% of inactive UC patients had similar profiles to those who were in an active state. This study demonstrates the possibilities of metabonomics as a diagnostic tool in active and quiescent UC and provides new insight into pathophysiologic mechanisms.

摘要

为了探索诊断的可能性、确定新的潜在生物标志物并深入了解病理生理学,我们对溃疡性结肠炎(UC)患者和对照者的结肠黏膜活检组织、结肠细胞、淋巴细胞和尿液进行了核磁共振(NMR)光谱分析和适当的多元统计分析。从活动期 UC 患者(n = 41)、缓解期 UC 患者(n = 33)和对照者(n = 25)中采集样本,并用 NMR 光谱进行分析。数据分析采用 SIMCA P+11 软件包(Umetrics,瑞典乌默奥)和 Matlab 环境进行主成分分析和正交偏最小二乘判别分析。在活检组织和结肠细胞的代谢谱中发现了对照者和活动期 UC 患者之间的显著差异。在活动期 UC 患者的活检组织中,抗氧化剂和多种氨基酸的水平较高,但脂质、甘油磷酸胆碱(GPC)、肌醇和甜菜碱的水平较低,而结肠细胞仅显示 GPC、肌醇和胆碱水平较低。有趣的是,20%的缓解期 UC 患者的特征与处于活动期的患者相似。本研究表明代谢组学作为活动期和缓解期 UC 的诊断工具具有一定的可能性,并为病理生理机制提供了新的见解。

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