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在部分身体照射小鼠模型中,血细胞计数和血液化学的短期和长期恢复动力学存在高度变异性。

High variability in short and long-term recovery kinetic of blood cell count and blood chemistry in a partial body irradiation mouse model.

机构信息

Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.

出版信息

Int J Radiat Biol. 2024;100(4):565-572. doi: 10.1080/09553002.2024.2304833. Epub 2024 Feb 2.

DOI:10.1080/09553002.2024.2304833
PMID:38306486
Abstract

PURPOSE

In the aftermath of a nuclear disaster or accident, survivors will suffer from radiation-induced normal tissue damage. Recovery after radiation exposure is dictated by several factors, one of which is degree of shielding at time of exposure. This study aims to characterize the short and late term changes in kinetics and magnitude of pancytopenia and blood chemistry in a model of heterogeneous radiation exposure, or partial body irradiation (PBI), compared to whole body irradiation (WBI).

MATERIALS AND METHODS

Male C57BL/6 mice, 8-10 weeks of age, were WBI at 6 different doses (6, 6.1. 6.15, 6.2, 6.5, and 7.5 Gy) to establish the LD. To determine the effect of shielding on blood cell counts and chemistry, animals were either WBI at 6 Gy (LD30) or 6 Gy PBI with one leg shielding (LD30). Complete blood counts and chemistry were measured at 1, 5-, 10-, 20-, 30- and 120-days post-irradiation.

RESULTS AND CONCLUSIONS

Irradiated animals had significant depletion of white blood cells, red blood cells and platelets up to 10 days post-irradiation. Separation between PBI and WBI were observed at 10- and 20-days post-irradiation at which point PBI animals showed sign of recovery while overall cell count remains depleted in WBI animals up to 30 days post-irradiation. In addition, significant changes were found in parameters indicative of hematopoietic injury including hemoglobin count, hematocrit count and white blood cell population. Significant changes were observed in kidney function with changes to blood urea nitrogen and calcium concentration at 5-days post-irradiation. At 10-days post-irradiation. liver function changes differentiated WBI from PBI animals. Long-term, irradiated animal's chemistry values and many blood counts were not significantly different from Sham. In conclusion, partial shielding ensured complete survival and demonstrated a different recovery kinetics of blood and chemistry parameters after irradiation compared to survivors of whole body irradiation and no single hemopoietic parameter was able to consistently differentiate irradiated from Sham animals. This seems to indicate that there is no single robust hemopoietic parameter to differentiate those exposed from those who were not due to the inherent variability in individual responses. Furthermore, there were no significant long-term effects on these blood parameters between survivors of WBI and PBI except that shielding accelerated recovery.

摘要

目的

在核灾难或事故发生后,幸存者将遭受辐射引起的正常组织损伤。辐射暴露后的恢复由几个因素决定,其中一个因素是暴露时的屏蔽程度。本研究旨在比较异质性辐射暴露(部分体照射,PBI)与全身照射(WBI)模型中,照射后短期和晚期全血细胞减少症和血液化学变化的特点。

材料和方法

雄性 C57BL/6 小鼠,8-10 周龄,分别接受 6 个不同剂量(6、6.1、6.15、6.2、6.5 和 7.5Gy)的 WBI,以确定 LD。为了确定屏蔽对血细胞计数和化学的影响,将动物 WBI 于 6Gy(LD30)或 6Gy PBI 并用一条腿屏蔽(LD30)。在照射后 1、5、10、20、30 和 120 天测量全血细胞计数和化学。

结果和结论

照射后的动物在照射后 10 天内白细胞、红细胞和血小板显著减少。在照射后 10 天和 20 天,PBI 和 WBI 之间有明显的分离,此时 PBI 动物开始恢复,而 WBI 动物的总细胞计数在照射后 30 天内仍然减少。此外,发现了与造血损伤相关的参数显著变化,包括血红蛋白计数、血细胞比容计数和白细胞计数。在照射后 5 天,肾功能发生显著变化,血尿素氮和钙浓度发生变化。在照射后 10 天,肝功能变化将 WBI 动物与 PBI 动物区分开来。长期来看,照射动物的化学值和许多血液计数与假手术动物无显著差异。总之,部分屏蔽确保了完全存活,并在照射后显示出与全身照射幸存者不同的血液和化学参数恢复动力学,没有单个造血参数能够始终如一地将照射后的动物与假手术动物区分开来。这似乎表明,由于个体反应的固有变异性,不存在单一可靠的造血参数来区分那些暴露于辐射的人和那些没有暴露于辐射的人。此外,WBI 和 PBI 幸存者之间除了屏蔽加速恢复外,这些血液参数没有长期影响。

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