基于代谢组学方法筛选大鼠血浆辐射敏感代谢物

doi:10.3969/j.issn.1004-616x.2020.03.002

癌变·畸变·突变 ›› 2020, Vol. 32 ›› Issue (3): 166-170,176.doi: 10.3969/j.issn.1004-616x.2020.03.002

基于代谢组学方法筛选大鼠血浆辐射敏感代谢物

赵骅, 陆雪, 蔡恬静, 李爽, 田梅, 刘青杰

中国疾病预防控制中心辐射防护与核安全医学所, 辐射防护与核应急中国疾病预防控制中心重点实验室, 北京 100088

收稿日期:2020-01-09 修回日期:2020-03-31 出版日期:2020-05-31 发布日期:2020-06-03
通讯作者: 刘青杰,E-mail:liuqingjie@nirp.chinacdc.cn E-mail:liuqingjie@nirp.chinacdc.cn
作者简介:赵骅,E-mail:zhaohua@nirp.chinacdc.cn。
基金资助:
国家自然科学基金（81573081）

Screening for radiation-sensitive biomarkers in rat plasma based on metabolomics studies

ZHAO Hua, LU Xue, CAI Tianjing, LI Shuang, TIAN Mei, LIU Qingjie

National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, Beijing 100088, China

Received:2020-01-09 Revised:2020-03-31 Online:2020-05-31 Published:2020-06-03

摘要/Abstract

摘要： 目的：筛选大鼠血浆辐射敏感代谢物并探索其代谢通路，为辐射损伤生物标志物研究提供科学依据。方法：用⁶⁰Co γ射线对20只大鼠进行全身照射，照射剂量分别为0、1、3、5 Gy，剂量率为1 Gy/min，采用基于液相色谱质谱串联平台的非靶向代谢组学方法，检测大鼠受照7 d后血浆中代谢物的变化。结果：大鼠受照后，筛选出血浆中11个辐射敏感代谢物，主要涉及牛磺酸和亚牛磺酸代谢、烟酸和烟酰胺代谢、初级胆汁酸生物合成等代谢通路。十八二烯酰基肉碱、十八一烯酰基肉碱、十六酰基肉碱、牛磺酸、L-犬尿氨酸及胞嘧啶随受照剂量的上升而显著下降（P < 0.05），具有明显的剂量-效应关系。结论：大鼠受到γ射线照射后，血浆中代谢物水平发生显著变化，有6个代谢物具备成为辐射生物剂量计的基础条件。

关键词: 代谢组学, 电离辐射, 生物标志物, 剂量效应

Abstract: OBJECTIVE: To screen for radiation-sensitive metabolites in rat plasma and to explore the metabolic pathways that provide scientific basis for identification of radiation-sensitive biomarkers. METHODS: Rats irradiated whole-body with ⁶⁰Co gamma rays of 0,1,3 and 5 Gy,respectively. Changes of metabolites in rat plasma were detected by non-targeted metabolomics method based on the liquid chromatography mass spectrometry platform. RESULTS: Eleven plasma metabolites were identified as the potential radiation biomarkers. Taurine and hypotaurine metabolism,nicotinic acid and nicotinamide metabolism,and primary bile acid biosynthesis were enriched after irradiation. Linoelaidylcarnitine,11Z-octadecenylcarnitine,L-palmitoylcarnitine,taurine,niacinamide,L-kynurenine and cytosine were decreased with the increased dose and had good dose-response relationships. CONCLUSION: The metabolites levels in rat plasma were significantly changed after exposure to gamma-rays. Six metabolites had the basic conditions for radiation biological dosimeters.

Key words: metabolomics, ionizing radiation, biomarker, dose response

中图分类号:

R144.1

赵骅, 陆雪, 蔡恬静, 李爽, 田梅, 刘青杰. 基于代谢组学方法筛选大鼠血浆辐射敏感代谢物[J]. 癌变·畸变·突变, 2020, 32(3): 166-170,176.

ZHAO Hua, LU Xue, CAI Tianjing, LI Shuang, TIAN Mei, LIU Qingjie. Screening for radiation-sensitive biomarkers in rat plasma based on metabolomics studies[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(3): 166-170,176.

参考文献

[1] BAZAN J G, CHANG P, BALOG R, et al. Novel human radiation exposure biomarker panel applicable for population triage[J]. Int J Radiat Oncol Biol Phys, 2014, 90(3):612-619.
[2] CHAUDHRY M A. Biomarkers for human radiation exposure[J]. J Biomed Sci, 2008, 15(5):557-563.
[3] LAIAKIS E C. Metabolomic applications in radiation biodosimetry[M]//High-Throughput Metabolomics. New York, NY:Springer New York, 2019:391-402.
[4] International Atomic Energy Agency. Cytogenetic dosimetry:Applications in preparedness for and response to radiation emergencies[R]. Vienna:EPR-biodosimetry, 2011:68-74.
[5] ROTHKAMM K, BEINKE C, ROMM H, et al. Comparison of established and emerging biodosimetry assays[J]. Radiat Res, 2013, 180(2):111-119.
[6] CASADEI L, VALERIO M, MANETTI C. Metabolomics:challenges and opportunities in systems biology studies[J]. Methods Mol Biol, 2018, 1702:327-336.
[7] JOHNSON C H, GONZALEZ F J. Challenges and opportunities of metabolomics[J]. J Cell Physiol, 2012, 227(8):2975-2981.
[8] WANT E J, WILSON I D, GIKA H, et al. Global metabolic profiling procedures for urine using UPLC-MS[J]. Nat Protoc, 2010, 5(6):1005-1018.
[9] GOLLA S, GOLLA J P, KRAUSZ K W, et al. Metabolomic analysis of mice exposed to Gamma radiation reveals a systemic understanding of total-body exposure[J]. Radiat Res, 2017, 187(5):612-629.
[10] MAK T D, TYBURSKI J B, KRAUSZ K W, et al. Exposure to ionizing radiation reveals global dose- and time-dependent changes in the urinary metabolome of rat[J]. Metabolomics, 2015, 11(5):1082-1094.
[11] TANG X X, ZHENG M C, ZHANG Y Y, et al. Estimation value of plasma amino acid target analysis to the acute radiation injury early triage in the rat model[J]. Metabolomics, 2013, 9(4):853-863.
[12] CHEEMA A K, MEHTA K Y, RAJAGOPAL M U, et al. Metabolomic studies of tissue injury in nonhuman Primates exposed to Gamma-radiation[J]. Int J Mol Sci, 2019, 20(13):E3360.
[13] LAIAKIS E C, NISHITA D, BUJOLD K, et al. Salivary metabolomics of total body irradiated nonhuman Primates reveals long-term normal tissue responses to radiation[J]. Int J Radiat Oncol Biol Phys, 2019, 105(4):843-851.
[14] AYDıN A F,ÇOBAN J, DOǦAN-EKICI I, et al. Carnosine and taurine treatments diminished brain oxidative stress and apoptosis in D-galactose aging model[J]. Metab Brain Dis, 2016, 31(2):337-345.
[15] SEIDMAN L J, SHAPIRO D I, STONE W S, et al. Association of neurocognition with transition to psychosis:baseline functioning in the second phase of the north American prodrome longitudinal study[J]. JAMA Psychiatry, 2016, 73(12):1239-1248.
[16] VON SCHÖNFELS W, PATSENKER E, FAHRNER R, et al. Metabolomic tissue signature in human non-alcoholic fatty liver disease identifies protective candidate metabolites[J]. Liver Int, 2015, 35(1):207-214.
[17] BASARANOGLU M, BASARANOGLU G, SENTüRK H. From fatty liver to fibrosis:a tale of "second hit"[J]. World J Gastroenterol, 2013, 19(8):1158-1165.
[18] SCHWARCZ R, BRUNO J P, MUCHOWSKI P J, et al. Kynurenines in the mammalian brain:when physiology meets pathology[J]. Nat Rev Neurosci, 2012, 13(7):465-477.
[19] PATTI G J, YANES O, SIUZDAK G. Innovation:Metabolomics:the apogee of the omics trilogy[J]. Nat Rev Mol Cell Biol, 2012, 13(4):263-269.
[20] KULTOVA G, TICHY A, REHULKOVA H, et al. The hunt for radiation biomarkers:current situation[J]. Int J Radiat Biol, 2020, 96(3):370382.

基于代谢组学方法筛选大鼠血浆辐射敏感代谢物

Screening for radiation-sensitive biomarkers in rat plasma based on metabolomics studies

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	向嘉琪, 孙佳丽, 王成芳, 刘青杰, 田梅. ⁶⁰Co γ射线全身照射大鼠尿液的非标记定量蛋白质组学分析[J]. 癌变·畸变·突变, 2021, 33(3): 172-177,192.
[2]	陆雪, 田雪蕾, 赵骅, 蔡恬静, 田梅, 刘青杰. 人外周血淋巴细胞微核分析用于估算离体模拟局部照射剂量的研究[J]. 癌变·畸变·突变, 2021, 33(3): 193-196.
[3]	张玉领, 陈培. 环状RNA在食管癌中的研究进展[J]. 癌变·畸变·突变, 2021, 33(3): 241-245.
[4]	徐海明, 刘科良, 郝艳星, 汪岭, 刘志宏, 德小明. 生物标志物的联合检测对矽肺早期辅助诊断的价值[J]. 癌变·畸变·突变, 2020, 32(5): 395-397,401.
[5]	李爽, 陆雪, 封江彬, 田梅, 蔡恬静, 刘青杰. 性别和年龄对⁶⁰Co γ射线照射离体人外周血辐射敏感基因mRNA表达的影响[J]. 癌变·畸变·突变, 2019, 31(6): 421-427.
[6]	田雪蕾, 封江彬, 田梅, 刘青杰. 甲基化芯片检测电离辐射诱导人外周血淋巴细胞DNA甲基化水平的变化[J]. 癌变·畸变·突变, 2019, 31(6): 434-439.
[7]	肖瑶, 王美杰, 侯绍英. UPLC/Q-TOF MS/MS技术评价防腐剂硼酸和叠氮化钠对尿液代谢物的影响[J]. 癌变·畸变·突变, 2018, 30(6): 442-446,451.
[8]	高延晓, 田梅, 高刚, 刘建香. 降扎乡高氡温泉周围居民血浆中8-羟基脱氧鸟苷和硫氧还蛋白还原酶水平的研究[J]. 癌变·畸变·突变, 2018, 30(3): 226-229.
[9]	曲功霖, 李辰, 邵帅, 王春燕, 齐雪松, 佟鹏, 李宁. 四君子汤对电离辐射损伤的防治作用[J]. 癌变·畸变·突变, 2017, 29(4): 295-299.
[10]	王乐乐, 刘江正, 刘萌萌, 孔德钦, 张涛, 于卫华, 刘瑞, 张晓迪, 王欣, 海春旭. 镉暴露致大鼠肾损伤的量效关系及其机制[J]. 癌变·畸变·突变, 2016, 28(6): 446-452.
[11]	郑剑, 蓝涛, 刘威, 邓荣霞, 李培茂, 张艳芳, 刘建军. 三氯乙烯药疹样皮炎患者血清miRNAs差异表达谱分析[J]. 癌变·畸变·突变, 2016, 28(6): 468-471.
[12]	张忠新, 张睿凤, 张慧芳, 段志凯. 常用辐射生物剂量计的研究现状[J]. 癌变·畸变·突变, 2016, 28(4): 325-328.
[13]	杨英杰, 刘建香, 高刚. 电离辐射对小鼠外周血单核细胞亚群的影响[J]. 癌变·畸变·突变, 2016, 28(4): 298-301.
[14]	高志奎, 刘冉, 尹立红, 浦跃朴. miR-338基因簇与食管癌发病风险的病例对照研究[J]. 癌变·畸变·突变, 2016, 28(2): 107-110.
[15]	许文黎, 岳娟, 袁慧, 黄立群, 王新钢, 王永丽, 闻建华. 氮氧自由基在辐射防护中的应用[J]. 癌变·畸变·突变, 2015, 27(6): 490-492.