慢性高原病患者血清GC-TOF-MS代谢组学的初步研究  

Preliminary study of patients with chronic mountain sickness by GC-TOF-MS based serum metabolomics analysis

作　　者：曹学锋[1] 白振忠[1] 马兰[1] 马爽[1] 格日力[1] 

机构地区：[1]a青海大学医学院高原医学研究中心,青海西宁810001

出　　处：《中国病理生理杂志》2017年第9期1676-1682,共7页Chinese Journal of Pathophysiology

基　　金：国家重点基础研究发展计划(973计划)项目(No.2012CB518200);国家自然科学基金资助项目(No.31571231);青海-犹他联合重点实验室项目(No.2014-ZJ-Y39);青海大学医学院中青年科研基金资助项目(No.2015-KY-2)

摘　　要：目的:研究慢性高原病患者气相色谱飞行时间质谱(GC-TOF-MS)代谢组学的变化,并鉴定血清代谢图谱的内源性代谢物,探讨青海玉树世居藏族居民潜在的差异性代谢标志物。方法:收集10例青海玉树世居藏族慢性高原病患者(CMS组)和10例世居高原健康藏族居民(control组)血清,利用GC-TOF-MS代谢组学和多元回归分析方法,如主成分分析法(PCA)、偏最小二乘法判别分析(PLS-DA)和正交偏最小二乘法判别分析(OPLS-DA)模式识别分析各代谢物的变化。结果:PCA、PLS-DA和OPLS-DA模式判别分析结果显示,两组血清代谢组均表现出明显聚类型分布。CMS组血清中延胡索酸、肌苷、植烷酸、2,2-二甲基丁二酸、β-酮己二酸、异亮氨酸、甘氨酸、丝氨酸、L-半胱氨酸、瓜氨酸、三甲基赖氨酸、1-磷酸葡萄糖和核糖水平显著高于control组;CMS组血清中下降的代谢物有硫酸、草酸、谷氨酰胺和来苏糖。结论:慢性高原病患者和高原健康藏族居民血清代谢物水平有显著性差异,这些血清代谢物的改变可能参与了慢性高原病的发生与发展。AIM： To evaluate specific metabolomics profiles in the serum of patients with chronic mountain sickness（ CMS） and to explore the potential metabolic biomarkers in the native Tibetans living on the Qinghai-Tibet Plateau. METHODS： A gas chromatography time-of-flight mass spectrometry（ GC-TOF-MS） approach as a metabolomics technique was used to evaluate metabolic differences. The native Tibetan CMS patients（ n = 10） and healthy Tibetan controls（ n = 10） were enrolled from Yu Shu in Qinghai province in this study. The serum samples were collected and analyzed by GC-TOF-MS coupled with a series of multivariate statistical analyses such as principal component analysis（ PCA）,partial least squares discriminant analysis（ PLS-DA） and orthogonal partial least squares discriminant analysis（ OPLS-DA）.RESULTS： The intergroup differences between CMS patients and control subjects have been observed. A list of differential metabolites and several top altered metabolic pathways have been identified. The levels of fumaric acid,an intermediate in the tricarboxylic acid（ TCA） cycle,and inosine were highly upregulated in the CMS patients,suggesting a greater effort to hypoxic adaptation in high elevation area. Other differential metabolites,such as methyl phosphate,2-ketoadipate,lyxose and phytanic acid were also identified. Importantly,the differential metabolites possessed higher area under the ROC curve（AUC） values,indicating an excellent clinical ability for the prediction of CMS. Increased levels of amino acids（isoleucine,glycine,serine,L-cysteine,citrulline and trimethyllysine） were detected in CMS group,yet significantly decreased levels of sulfuric acid,oxamic acid,lyxose and glutamine were also detected in CMS group than those in control group. At the same time,the levels of ribose and glucose-1-phosphate were markedly elevated in CMS group（ P 0. 05）. CONCLUSION： The metabolic activities are significantly altered in the serum of CMS patients. High altitude hypoxia may act on

关 键 词：慢性高原病 气相色谱飞行时间质谱 代谢组学 

分 类 号：R363[医药卫生—病理学]