摘要
目的探索全身照射大鼠血浆代谢物变化,为辐射生物标志物研究提供实验依据。方法应用代谢组学方法筛选辐射差异代谢物并进行初步验证。筛选研究中,大鼠50只(发现集),用60Coγ射线对大鼠进行全身照射,照射剂量为0、1、2、3、5、8 Gy;验证研究中,大鼠25只(验证集),照射剂量为0、0.5、2.5、4、6 Gy。照射后4 h采集外周血液,分离血浆进行代谢组学分析,并测定辐射差异代谢物浓度,用代谢物组合受试者工作特征曲线(ROC)对特定剂量进行分类。结果共筛选出8个血浆辐射差异代谢物,其中4个(胞嘧啶、己酰基肉碱、十八碳二烯酰基肉碱及棕榈酰基肉碱)在受照后发生上调,变化趋势与验证集一致,区分特定剂量样本曲线下面积(AUC)>0.75。将上述4个代谢物进行组合后,区分0 Gy与>0 Gy、<2 Gy与≥2 Gy、<5 Gy与≥5 Gy样本的AUC值分别为0.96、1和0.94。结论大鼠受到全身照射后4 h,血浆代谢物发生显著变化,共鉴定出8个辐射差异代谢物,其中胞嘧啶、己酰基肉碱、十八碳二烯酰基肉碱及棕榈酰基肉碱具有良好的稳定性,其组合具有较高的分类准确性,有可能成为特定剂量分类的辐射敏感标志物。
Objective To investigate the metabolite changes in rat plasma after total body irradiation(TBI)and to explore dose classification based on radiation sensitive metabolites.Methods The differential metabolites induced by radiation were screened and verified by metabolomics.In the discovery stage,50 SD rats were irradiated with 0,1,2,3,5 and 8 Gy of 60Coγ-rays.In the verification stage,25 rats were irradiated with 0,0.5,2.5,4 and 6 Gy.Peripheral blood samples were collected 4 h after irradiation,and plasma was separated.Radiation-induced differential metabolites were identified and their concentrations were determined.Receiver operating characteristic(ROC)curve of the differential metabolites was used to classify dose range.Results In the discovery stage,8 radiation-induced differential metabolites in rat plasma were identified and four of them(cytosine,L-hexylcarnitine,Linoelaidylcarnitine and L-palmitylcarnitine)were upregulated,which was confirmed in the verification stage.The area under the curve(AUC)for the specific dose was>0.75.After combining these four metabolites,the AUC value to classify the radiation dose of 0 Gy versus>0 Gy,<2 Gy versus≥2 Gy,<5 Gy versus≥5 Gy were 0.96,1 and 0.94,respectively.Conclusions The metabolites in rat plasma changed significantly at 4 h after TBI,where 8 differential metabolites were identified.Cytosine,L-hexylcarnitine,linoelaidylcarnitine and L-palmiylcarnitine were stably over-expressed in the plasma after irradiation.The combination of these four compounds had high classification accuracy and thus may applicable as radiation sensitive biomarkers for dose classification.
作者
赵骅
习聪
田雪蕾
刘海翔
田梅
刘青杰
Zhao Hua;Xi Cong;Tian Xuelei;Liu Haixiang;Tian Mei;Liu Qingjie(Key Laboratory of Radiological Protection and Nuclear Emergency,China CDC,National Institute for Radiological Protection,Chinese Center for Disease Control and Prevention,Beijing 100088,China)
出处
《中华放射医学与防护杂志》
CAS
CSCD
北大核心
2021年第6期401-406,共6页
Chinese Journal of Radiological Medicine and Protection
基金
国家自然科学基金(82003393,81573081)。
