| 张俊,胡文涛,许志明,等.超高剂量率照射与常规照射后胶质瘤小鼠血浆代谢物时序性特征对比分析[J].中华放射医学与防护杂志,2023,43(10):759-765.Zhang Jun,Hu Wentao,Xu Zhiming,et al.Comparative analysis of the temporal characteristics of plasma metabolites in glioma mice after ultra-high dose rate radiation and conventional radiation[J].Chin J Radiol Med Prot,2023,43(10):759-765 |
| 超高剂量率照射与常规照射后胶质瘤小鼠血浆代谢物时序性特征对比分析 |
| Comparative analysis of the temporal characteristics of plasma metabolites in glioma mice after ultra-high dose rate radiation and conventional radiation |
| 投稿时间：2023-03-30 |
| DOI：10.3760/cma.j.cn112271-20230330-00102 |
| 中文关键词: 超高剂量率照射 常规照射 胶质瘤 生物标志物 |
| 英文关键词:Ultra-high dose rate radiation Conventional radiation Glioma Biomarker |
| 基金项目:省部共建放射医学与辐射防护国家重点实验室开放课题(GZK1202221);苏州大学附属第二医院核技术医学应用重点人才项目(XKTJ-HRC2021002) |
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| 中文摘要: |
| 目的 探究超高剂量率照射(FLASH-RT)和常规照射(CONV-RT)对胶质瘤小鼠血浆代谢物的影响。方法 胶质瘤模型雄性C57BL/6J小鼠21只,按随机数表法分成健康对照组(3只)、CONV-RT组(9只)和FLASH-RT组(9只)。CONV-RT组以0.4 Gy/s的剂量率对小鼠头部进行单次24 Gy照射,FLASH-RT组以60 Gy/s的剂量率对小鼠头部进行单次24 Gy照射,健康对照组以相同条件给予0 Gy假照射。两照射组照射后1、3、7 d分别收集小鼠眼内眦静脉血并分离血浆。健康对照组于假照射后7 d收集小鼠眼内眦静脉血并分离血浆。采取基于液相色谱质谱串联平台的非靶向代谢组学方法检测胶质瘤小鼠血浆代谢物的变化。结果 胶质瘤小鼠受不同方式照射后,血浆中代谢物均发生显著变化。FLASH-RT组和CONV-RT组3个时间点分别与健康对照组相比筛选出12和5种差异代谢物,照后1 d血浆代谢物差异最大,照后3和7 d血浆代谢物差异减小。FLASH-RT组筛选出的花生四烯酸与异戊酸也存在于CONV-RT组中,其余10种差异代谢物仅存在FLASH-RT组,主要涉及能量代谢和氧化还原反应。FLASH-RT与CONV-RT组均涉及花生四烯酸代谢、不饱和脂肪酸的生物合成和酪氨酸代谢途径。结论 花生四烯酸与异戊酸有可能成为不同辐射方式共有的敏感标记物,为探索FLASH-RT治疗胶质瘤的分子机制提供思路。 |
| 英文摘要: |
| Objective To investigate the effects of ultra-high dose rate radiation (FLASH-RT) and conventional radiation (CONV-RT) on plasma metabolites in glioma mice. Methods Tocally 21 male C57BL/6J mice bearing intracranial glioma xenograft were randomly divided into healthy control group (n=3), CONV-RT group (n=9) and FLASH-RT group (n=9). The CONV-RT group was administered a single dose of 24 Gy radiation on the head of mice at a dose rate of 0.4 Gy/s, and the FLASH-RT group was administered a single dose of 24 Gy radiation on the head of mice at a dose rate of 60 Gy/s, and the healthy control group was given 0 Gy pseudoradiation under the same condition. Mice blood was collected through the inner canthus vein for plasma separation at 1, 3 and 7 d after radiation in the two radiation groups, and the blood plasma of healthy control group was collected at 7 days after sham radiation. The changes in plasma metabolites were detected by the non-targeted metabolomics based on liquid chromatography mass spectrometry tandem platform. Results After irradiation, the metabolites in plasma of two irradiation groups had significant difference. Compared with the healthy control group, 12 and 5 differential metabolites were screened out in the FLASH-RT group and CONV-RT group at three time points, respectively. The difference of plasma metabolites had the largest value at 1 day and decreased at 3 and 7 d after radiation. The arachidonic acid and isovaleric acid, involving arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, and tyrosine metabolism pathways were screened in both FLASH-RT group and CONV-RT group, and the 10 differential metabolites, mainly involving energy metabolism and redox reactions, only existed in the FLASH-RT group. Conclusions Arachidonic acid and isovaleric acid may be the common sensitive biomarkers to different radiation patterns, which provides ideas for further exploring the molecular mechanism of FLASH-RT in the treatment of glioma. |
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