基于GC/TOFMS测定技术的Wistar大鼠血浆代谢谱增龄性变化研究  

Metabonomic profiling of plasma metabolites in Wistar rats to study the effect of aging by means of GC/TOFMS-based techniques

作　　者：黄青[1,2] 陆益红[1,2] 王广基[2] 王新文[3] 孟楠[3] 高洁[3] 卢迪[3] 闫鑫[3] 张颖[2] 刘林生[2] 郝刚[2] 严蓓[2] 顾胜华[2] 阿基业[2] 

机构地区：[1]江苏省食品药品检验所,江苏南京210008 [2]中国药科大学药物代谢动力学重点实验室,江苏南京210009 [3]中国药科大学-大学生实践创新训练计划项目成员,江苏南京210009

出　　处：《药学学报》2009年第10期1095-1101,共7页Acta Pharmaceutica Sinica

摘　　要：研究Wistar大鼠血浆中小分子化合物随生长而产生的增龄性差异,揭示实验大鼠生长过程中机体内源性物质基础的变化规律。运用基于GC/TOFMS检测技术的代谢组学方法,分析Wistar模型大鼠12、14、16、18及20周龄时血浆中内源性小分子代谢物,经数据处理和模式识别后,不同周龄组的大鼠可被清晰区分并呈明显的动态变化轨迹。血浆中柠檬酸、乌头酸、十六碳烯酸、苯丙氨酸、羟脯氨酸、α-生育酚、精氨酸等代谢产物的相对含量发生了明显改变,提示为潜在的生物标志物,这些化合物与能量代谢、脂质过氧化、抗氧化平衡等密切相关。本研究一方面为探索实验大鼠生长过程中的生理变化及生物学本质提供了基础信息,此外还发现即便是生理学上正常的动物,其体内代谢水平(随生长有一定改变)也不是恒定不变的,提示在利用代谢组学、生物标志物评价药物毒性和药效时,需结合正常对照组的动态变化规律,以便作出独立于生长因素的正确判断。The global metabolite profiles of endogenous compounds of Wistar rats from 12 to 20 weeks old were investigated to take deep insight into and get better understanding of the pathogenesis of development and aging.Plasma from Wistar rats at 12,14,16,18,and 20 weeks old were analyzed using GC/TOFMS.Multivariate data analysis was then used to process the metabonomic data which indicated excellent separation between different weeks and showed that the metabolic profiles of the samples changed with age,enabling age-related metabolic trajectories to be visualized.Decreased concentrations of citric acid,cis-aconitic acid,9-（z）-hexadecenoic acid along with increased levels of hexanedioic acid,α-tocopherol,3-indole propionic acid,etc contributed to the separation.Several major metabolic pathways were identified to be involved in metabolic regulation.This suggests that GC/TOFMS-based metabonomics is a powerful alternative approach to identifying potential biomarkers and investigating the physiological developments of aging and it is important to employ suitable age-match control group in metabonomic study of physiological monitoring,drug safety assessment,and disease diagnosis,etc.

关 键 词：代谢组学 生长 气相色谱/飞行时间质谱 

分 类 号：R969.1[医药卫生—药理学]