评估通过与组织和组织学分析相关联，对非人类灵长类动物进行最小骨髓保留的全身局部照射后发生胃肠道急性放射综合征的血浆生物标志物的效用。
Evaluation of Plasma Biomarker Utility for the Gastrointestinal Acute Radiation Syndrome in Non-human Primates after Partial Body Irradiation with Minimal Bone Marrow Sparing through Correlation with Tissue and Histological Analyses.
机构信息
University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.
Epistem Ltd., Manchester, UK.
出版信息
Health Phys. 2020 Nov;119(5):594-603. doi: 10.1097/HP.0000000000001348.
Exposure to total- and partial-body irradiation following a nuclear or radiological incident result in the potentially lethal acute radiation syndromes of the gastrointestinal and hematopoietic systems in a dose- and time-dependent manner. Radiation-induced damage to the gastrointestinal tract is observed within days to weeks post-irradiation. Our objective in this study was to evaluate plasma biomarker utility for the gastrointestinal acute radiation syndrome in non-human primates after partial body irradiation with minimal bone marrow sparing through correlation with tissue and histological analyses. Plasma and jejunum samples from non-human primates exposed to partial body irradiation of 12 Gy with bone marrow sparing of 2.5% were evaluated at various time points from day 0 to day 21 as part of a natural history study. Additionally, longitudinal plasma samples from non-human primates exposed to 10 Gy partial body irradiation with 2.5% bone marrow sparing were evaluated at timepoints out to 180 d post-irradiation. Plasma and jejunum metabolites were quantified via liquid chromatography-tandem mass spectrometry and histological analysis consisted of corrected crypt number, an established metric to assess radiation-induced gastrointestinal damage. A positive correlation of metabolite levels in jejunum and plasma was observed for citrulline, serotonin, acylcarnitine, and multiple species of phosphatidylcholines. Citrulline levels also correlated with injury and regeneration of crypts in the small intestine. These results expand the characterization of the natural history of gastrointestinal acute radiation syndrome in non-human primates exposed to partial body irradiation with minimal bone marrow sparing and also provide additional data toward the correlation of citrulline with histological endpoints.
在核或放射性事件后，全身或局部暴露于辐射会导致胃肠道和造血系统出现潜在致命的急性辐射综合征，其方式与剂量和时间有关。放射性对胃肠道的损伤在照射后数天至数周内即可观察到。我们的研究目的是评估血浆生物标志物在非人类灵长类动物局部全身照射后胃肠道急性辐射综合征中的效用，方法是通过与组织和组织学分析相关联来实现对骨髓最小程度保存的评估。在一项自然史研究中，对接受局部全身照射 12 Gy 且骨髓保存 2.5%的非人类灵长类动物的血浆和空肠样本进行了评估，时间从 0 天到 21 天不等。此外，对接受局部全身照射 10 Gy 且骨髓保存 2.5%的非人类灵长类动物的纵向血浆样本进行了评估，时间延长至照射后 180 天。通过液相色谱-串联质谱法对血浆和空肠代谢物进行了定量分析，组织学分析包括校正隐窝数，这是一种评估放射性胃肠道损伤的既定指标。空肠和血浆中代谢物水平呈正相关，包括瓜氨酸、血清素、酰基肉碱和多种磷脂。瓜氨酸水平也与小肠隐窝的损伤和再生相关。这些结果扩展了对非人类灵长类动物局部全身照射且骨髓最小程度保存后胃肠道急性辐射综合征自然史的特征描述，并且还为瓜氨酸与组织学终点的相关性提供了更多数据。
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