Study on urine biomarkers of radiation-induced injury guided by Caenorhabditis elegans as a model organism

Q1 Health Professions Radiation Medicine and Protection Pub Date : 2021-09-01 DOI:10.1016/j.radmp.2021.08.001
Xin Wu, Tong Zhu, Hang Li, Xin He, Sai-jun Fan
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引用次数: 2

Abstract

Objective

Under the guidance of model organism Caenorhabditis elegans with fine olfactory system, small molecular metabolites sensitive to high dose radiation were screened as biomarkers of acute radiation-induced injury, and their metabolic pathways were elucidated by enrichment.

Methods

Rats were irradiated with 12 ​Gy γ-rays to establish an acute radiation injury model, and their urine was fingerprinted using UPLC-Q/TOF-MS. Further, under the guidance of Caenorhabditis elegans as olfactory-sensitive model organism, the key differential metabolites in urine were found as biomarkers of radiation-induced injury.

Results

After rats were irradiated, the radiation injury urine showed a difference from control (sham-irradiated) urine, which could be distinguished by Caenorhabditis elegans. Based on metabolomics analysis, a total of 21 key differential metabolites with P value ​< ​0.05 and fold change either >2 or <0.5 were identified, which can be used as sensitive and reliable biomarkers of radiation-induced injury. The pathways were further enriched, and it was found that disorders of five metabolic pathways, including citric acid cycle and amino acid metabolism, play an important role in radiation-induced injury.

Conclusions

Due to radiation injury, the metabolites in urine will change significantly. The study on biomarkers guided by model organism Caenorhabditis elegans provides a new perspective to explain the details of metabolic disorders, and also provides experimental basis for the development of new biological dosimeters.

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以秀丽隐杆线虫为模式生物引导的辐射损伤尿液生物标志物研究
目的在具有精细嗅觉系统的模式生物秀丽隐杆线虫的指导下,筛选对高剂量辐射敏感的小分子代谢物作为急性辐射损伤的生物标志物,并对其代谢途径进行富集研究。方法用12 Gy γ射线照射大鼠,建立急性辐射损伤模型,用UPLC-Q/TOF-MS对大鼠尿液进行指纹图谱分析。进一步,在秀丽隐杆线虫作为嗅觉敏感模式生物的指导下,发现尿液中的关键差异代谢物作为辐射损伤的生物标志物。结果大鼠辐照后的辐射损伤尿与对照(假辐照)尿存在差异,可通过秀丽隐杆线虫进行鉴别。基于代谢组学分析,共有21个关键差异代谢物具有P值<鉴定出0.05和>2或<0.5的折叠变化,可作为敏感可靠的辐射损伤生物标志物。途径进一步丰富,发现柠檬酸循环、氨基酸代谢等5种代谢途径紊乱在辐射损伤中起重要作用。结论辐射损伤后,尿中代谢物发生明显变化。以模式生物秀丽隐杆线虫为指导的生物标志物研究,为解释代谢紊乱的细节提供了新的视角,也为开发新型生物剂量计提供了实验依据。
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来源期刊
Radiation Medicine and Protection
Radiation Medicine and Protection Health Professions-Emergency Medical Services
CiteScore
2.10
自引率
0.00%
发文量
0
审稿时长
103 days
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