核磁共振氢谱代谢组学方法确定X射线对小鼠辐射的损伤  

Radiation metabolomics of minimally invasive urine biomarkers for X-ray radiation exposure in mice

作　　者：王敏[1] 潘晓婧[1] 刘斌[1,2] 张红[2] 

机构地区：[1]兰州大学,甘肃省兰州市730000 [2]中国科学院近代物理研究所,甘肃省兰州市730000

出　　处：《中国组织工程研究》2013年第46期8049-8055,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家重点基础研究发展计划资助(2010CB834202);国家自然科学基金重点项目(10835011);国家自然科学基金面上项目(30770639);兰州大学中央高校基本科研费2012年面上项目(lzujbky-2012-154);兰州大学口腔医学院扶持基金项目(120653)~~

摘　　要：背景:单一的血液学分析仅能针对辐射损伤后某个时间点机体的损伤情况,并不能反映机体辐射损伤后的较长期的累积状况。目的:采用基于核磁共振氢谱的代谢组学研究方法确定X射线对小鼠的辐射损伤后尿液和血液中辐射损伤标志物。方法:取小鼠48只随机分为4组,分别接受0(假辐射),3,9,27 Gy X射线头部辐射,分别于辐射后24 h和5 d后采血检测。另取小鼠36只随机分为3组,分别接受0(假辐射),9,27 Gy X射线头部辐射,分别于辐射前2 d和辐射后第5天收集24 h尿液检测。采集的血液及尿液进行1H-NMR分析。结果与结论:接受不同剂量X射线辐射后,血清中天冬氨氨基转移酶和丙氨酸氨基转移酶含量没有显著变化,碱性磷酸酶在9 Gy X射线辐射后有显著性升高,表明低剂量头部辐射可能引起肝脏或者骨骼中辐射损伤修复增加;血清中总超氧化物歧化酶在辐射后第5天出现显著降低,表明小鼠经头部辐射后引起了全身氧化应激效应。尿液中N-乙酰甘氨酸和-胸苷在接受各剂量X射线辐射后均显著升高,可以作为头部辐射后尿液中的辐射损伤标志物。尿液中3-羟基-2-甲基苯甲酸-3-氧硫酸盐在接受9 Gy X射线辐射后升高了2.5倍,可以作为中低剂量辐射损伤的特异标志物;尿液牛磺酸在27 Gy X射线辐射后升高20%,可以作为高剂量辐射损伤的特异标志物。BACKGROUND： Single hematology analysis can only reflect the body injury at a certain time point after radiation damage, but cannot reflect the longer-term cumulative status after radiation damage. OBJECTIVE： To identify the biomarkers in blood and urine in mice after radiation damage with metabolomics method based on nuclear magnetic resonance hydrogen spectrum. METHODS： Forty-eight mice were randomly divided into four groups and received 0 （sham radiation）, 3, 9 and 27 Gy radiation. The blood samples were collected at 24 hours and 5 days after radiation. Another 36 mice were collected and divided into three groups and received 0 （sham radiation）, 9 and 27 Gy radiation, then the urine samples were collected at 2 days before radiation and 5 days after radiation for 24 hours. The blood and urinesamples were analyzed with proton nuclear magnetic resonance spectroscopy, RESULTS AND CONCLUSION： The content of aspartic aminotransferase and alanine aminotransferase in blood plasma maintained a stable level after 3- or 9-Gy X-ray radiation, but the level of alkaline phosphatase in blood plasma was increased significantly after 9-Gy radiation, which indicating that low-dose head radiation may cause increased ,radiation damage and repair. The level of total superoxide dismutase in blood plasma was significantly decreased at 5 days after radiation which indicating that head radiation in mice could cause systemic oxidative stress. Meanwhile, the N-hexamolglycine and -thymidine level in the urine samples was significantly increased after different doses X-ray radiation, which can be used as the radiation damage markers in urine samples after head radiation. The 3-hydroxy-2-methylbenzoic acid 3-O-sulfate level in urine samples was increased by 2.5 times after received 9-Gy radiation, which can be used as the specific markers of middle- and low-dose radiation damage; the level of taurine in the urine samples was increased by 20% after 27-Gy radiation, which can be used as the specific markers of high-dose radiat

关 键 词：组织构建 组织构建细胞学实验 代谢组学 X射线 核磁共振氢谱 辐射损伤 碱性磷酸酶 超氧化物歧化酶 生物标志物 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]