中国组织工程研究 ›› 2013, Vol. 17 ›› Issue (46): 8049-8055.doi: 10.3969/j.issn.2095-4344.2013.46.012

• 组织构建细胞学实验 cytology experiments in tissue construction • 上一篇    下一篇

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

王  敏1,潘晓婧1,刘  斌1, 2,张  红2   

  1. 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
  • 出版日期:2013-11-12 发布日期:2013-11-30
  • 通讯作者: 刘斌,教授,兰州大学口腔医学院及中国科学院X射线束辐射生物医学重点实验室,甘肃省兰州市 730000 liubkq@lzu.edu.cn
  • 作者简介:王敏☆,男,1978年生,甘肃省天水市人,汉族,副教授,2011年四川大学生物治疗国家重点实验室毕业,博士,主要从事辐射生物学效应和药物临床前安全性评价研究。 wangmin@lzu.edu.cn
  • 基金资助:

    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)*

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

Wang Min1, Pan Xiao-jing1, Liu Bin 1, 2, Zhang Hong2   

  1. 1 Lanzhou University, Lanzhou  730000, Gansu Province, China; 2 Institute of Modern Physics, Chinese Academy of Science, Lanzhou  730050, Gansu Province, China
  • Online:2013-11-12 Published:2013-11-30
  • Contact: Liu Bin, Professor, Lanzhou University, Lanzhou 730000, Gansu Province, China; Institute of Modern Physics, Chinese Academy of Science, Lanzhou 730050, Gansu Province, China liubkq@lzu.edu.cn
  • About author:Wang Min☆, M.D., Lanzhou University, Lanzhou 730000, Gansu Province, China wangmin@lzu.edu.cn
  • Supported by:

    Major State Basic Research Development Program of China, No. 2010CB834202*; Key Program of National Natural Science Foundation of China, No. 10835011*; General Project of National Natural Science Foundation of China, No. 30770639*; Fundamental Research Funds for the Central Universities, Lanzhou University, No. lzujbky-2012-154*; Support Fund Project of Lanzhou University School of Stomatology, No.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。

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

Abstract:

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 urine samples 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 radiation damage. 

Key words: metabolome, magnetic resonance spectroscopy, radiation injuries, alkaline phosphatase, superoxide dismutase

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