Kiang Juliann G, Zhai Min, Liao Pei-Jyun, Bolduc David L, Elliott Thomas B, Gorbunov Nikolai V
Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA ; Department of Radiation Biology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA ; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA.
Oxid Med Cell Longev. 2014;2014:481392. doi: 10.1155/2014/481392. Epub 2014 Mar 5.
Exposure to ionizing radiation alone (radiation injury, RI) or combined with traumatic tissue injury (radiation combined injury, CI) is a crucial life-threatening factor in nuclear and radiological accidents. As demonstrated in animal models, CI results in greater mortality than RI. In our laboratory, we found that B6D2F1/J female mice exposed to (60)Co-γ-photon radiation followed by 15% total-body-surface-area skin burns experienced an increment of 18% higher mortality over a 30-day observation period compared to irradiation alone; that was accompanied by severe cytopenia, thrombopenia, erythropenia, and anemia. At the 30th day after injury, neutrophils, lymphocytes, and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were similar to basal levels. Comparing CI and RI mice, only RI induced splenomegaly. Both RI and CI resulted in bone marrow cell depletion. It was observed that only the RI mice treated with pegylated G-CSF after RI resulted in 100% survival over the 30-day period, and pegylated G-CSF mitigated RI-induced body-weight loss and depletion of WBC and platelets. Peg-G-CSF treatment sustained RBC balance, hemoglobin levels, and hematocrits and inhibited splenomegaly after RI. The results suggest that pegylated G-CSF effectively sustained animal survival by mitigating radiation-induced cytopenia, thrombopenia, erythropenia, and anemia.
单独暴露于电离辐射(辐射损伤,RI)或与创伤性组织损伤联合暴露(辐射复合伤,CI)是核事故和放射事故中危及生命的关键因素。如动物模型所示,CI导致的死亡率高于RI。在我们实验室,我们发现,B6D2F1/J雌性小鼠先接受(60)Co-γ光子辐射,随后全身15%体表面积皮肤烧伤,在30天观察期内,与单纯照射相比,死亡率增加了18%;同时伴有严重的血细胞减少、血小板减少、红细胞减少和贫血。在损伤后第30天,存活的RI和CI小鼠的中性粒细胞、淋巴细胞和血小板仍然很低。相比之下,它们的红细胞、血红蛋白和血细胞比容与基础水平相似。比较CI和RI小鼠,只有RI诱导脾肿大。RI和CI均导致骨髓细胞耗竭。观察到,只有RI后用聚乙二醇化G-CSF治疗的RI小鼠在30天内100%存活,且聚乙二醇化G-CSF减轻了RI诱导的体重减轻以及白细胞和血小板的耗竭。聚乙二醇化G-CSF治疗维持了RI后红细胞平衡、血红蛋白水平和血细胞比容,并抑制了脾肿大。结果表明,聚乙二醇化G-CSF通过减轻辐射诱导的血细胞减少、血小板减少、红细胞减少和贫血有效地维持了动物的存活。