金黄地鼠动脉粥样硬化发展过程中的NMR代谢组学研究  被引量:24

A 1H NMR based metabonomics approach to progression of coronary atherosclerosis in a hamster model

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作  者:江春迎 杨康敏 杨柳 苗朝霞 王映红 朱海波 

机构地区:[1]中国医学科学院、北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,“新药作用机制研究与药效评价”北京市重点实验室,北京100050

出  处:《药学学报》2013年第4期495-502,共8页Acta Pharmaceutica Sinica

基  金:国家“重大新药创制”科技重大专项(2009ZX09311-004,2012ZX09301002-004,2012ZX09102101-020);国家自然科学基金资助项目(30973527,81273514);北京市自然科学基金资助项目(7122114,7102115,NO.BZ0150);北京市优秀人才计划(2011A009008000004)

摘  要:采用核磁共振代谢组学法,动态观察金黄地鼠动脉粥样硬化过程中的代谢轮廓的改变,寻找动脉粥样硬化演进过程中的生物标志物。运用高脂饲料喂饲法复制金黄地鼠动脉粥样硬化模型,并收集不同时间点的血样,采用核磁共振波谱仪检测并进行主成分分析。研究结果表明,随着造模时间的推进,金黄地鼠血浆代谢轮廓呈现动态演变,在动脉粥样硬化进展中,不仅其脂质代谢发生了紊乱,而且还伴随着糖代谢、氨基酸代谢的紊乱以及炎症和氧化应激的出现。该研究加深了对动脉粥样硬化发病机制的认识,说明代谢组学是研究该疾病的有效手段。To obtain a better understanding of the progression of atherosclerosis and identify potential biomarkers, proton nuclear magnetic resonance spectroscopy (IH NMR)-based metabonomics was used to study the metabolic changes in the plasma of hamster fed with a high-fat/cholesterol diet. Plasma samples were collected at different time points during the progression of atherosclerosis and individual proton NMR spectra were visually and statistically assessed using multivariate analyses. NMR results for all samples showed a time-dependent development from physiological to pathophysiological status during atherosclerosis. Analysis of the identified biomarkers of atherosclerosis suggests that lipid and amino acid metabolisms are significantly disturbed, together with inflammation, oxidative stress, following cholesterol overloading. The results enriched our understanding of the mechanism of atherosclerosis and demonstrated the effectiveness of the NMR-based metabonomics approach to study such a complex disease.

关 键 词:动脉粥样硬化 金黄地鼠 代谢组学 核磁共振 

分 类 号:R969[医药卫生—药理学]

 

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