Purpose: Animal models that accurately reflect human responses to radiation injury are needed for advanced mechanistic investigation and development of effective therapeutics. The rabbit is an established animal model accepted by the FDA for studies of cardiovascular disease, lipid metabolism, the development of anticoagulants, testing of bone implants, and the development of treatments for infectious diseases such as HIV. The purpose of this study was to investigate the New Zealand White (NZW) Rabbit model as a model of acute radiation exposure because of its established similarity to human vascular, immune, and coagulation responses.

Materials & Methods: Two sequential studies were performed in a total of 81 male NZW rabbits, 16-20 weeks of age. All animals underwent clinical observations and peripheral blood analyses following a single dose of 0, 6,7,8,8.5, 9, or 10 Gy of total body irradiation via a 6 MV Linear accelerator photon source on Day 0. Animals were treated with timed release fentanyl patch (Day 0-30), subcutaneous hydration (Day 1, Study 2 only), and oral sulfamethoxazole/trimethoprim 30mg/kg once daily (Days 3-30) and were followed for 30 days or to time of mortality.

Results: Study 1 revealed the estimated LD30, -50, -70, and -90 with 95% confidence intervals (CI) at 30 days to be 6.7 (CI:5.9-7.4) , 7.3 (CI:6.7-7.8), 7.9 (CI: 7.3-8.4), and 8.8 (CI: 7.9-9.7) Gy respectively. In study 2, a survey of blood coagulation and biochemical parameters were performed over time and necropsy. Complete blood counts taken from animals exposed to 7, 8, or 10 Gy, demonstrated dose-dependent depletion of lymphocytes, neutrophils, and platelets. Platelet counts recovered to baseline levels in survivors by Day 30, whereas lymphocyte and neutrophil counts did not. Decedent animals demonstrated Grade 3 or 4 neutropenia and lymphopenia at time of death; 64% of the decedents experienced a 30% or greater drop in hematocrit. Decedent animals demonstrated more than 100% increases from serum baseline levels of blood urea nitrogen, creatinine, aspartate aminotransferase, and triglyceride levels at the time of death whereas survivors on average demonstrated modest or no elevation.

Conclusion: This NZW rabbit model demonstrates dose-dependent depletion of hematopoietic parameters. The LD_50/30 of 7.8 Gy (95% CI: 6.6-8.4) with supportive care appears to be close to the ranges reported for rhesus macaques (5.25-7.44 Gy) and humans (6-8 Gy) with supportive care. These findings support the utility of the NZW rabbit model for further mechanistic investigation of acute radiation exposure and medical countermeasure testing.

目的：需要精确反映人类对放射损伤反应的动物模型，以进行先进的机械研究和开发有效的治疗方法。兔子是美国食品与药物管理局（FDA）接受的用于研究心血管疾病，脂质代谢，开发抗凝剂，测试骨植入物以及开发感染性疾病（例如HIV）的动物模型。这项研究的目的是研究新西兰白（NZW）兔模型作为急性辐射暴露的模型，因为它与人类血管，免疫和凝血反应具有相似性。

材料与方法：在总共81只16-20周大的NZW雄性兔子中进行了两次连续研究。在第0天通过6 MV线性加速器光子源对全身进行单次剂量0、6、7、8、8.5、9或10 Gy辐射后，对所有动物进行临床观察和外周血分析。对动物进行定时治疗释放芬太尼贴剂（0-30天），皮下补水（仅第1天，研究2）和口服磺胺甲恶唑/甲氧苄氨嘧啶30mg / kg每天一次（3-30天），随访30天或直至死亡。

结果：研究1显示，在30天时具有95％置信区间（CI）的估计LD30，-50，-70和-90为6.7（CI：5.9-7.4），7.3（CI：6.7-7.8），7.9（CI ：7.3-8.4）和8.8（CI：7.9-9.7）Gy。在研究2中，随时间推移和尸检对血液凝固和生化参数进行了调查。从暴露于7 Gy，8 Gy或10 Gy的动物身上采集的全血细胞计数显示出淋巴细胞，中性粒细胞和血小板的剂量依赖性消耗。到第30天，血小板计数恢复到存活者的基线水平，而淋巴细胞和中性粒细胞计数没有恢复。后代动物在死亡时表现出3或4级中性粒细胞减少和淋巴细胞减少。64％的后裔血细胞比容下降了30％或更多。后代动物的血尿素氮，肌酐，

结论：该NZW兔模型证明了造血参数的剂量依赖性消耗。LD _50/30的7.8 Gy（95％CI：6.6-8.4）在支持治疗下似乎接近恒河猴（5.25-7.44 Gy）和人类（6-8 Gy）在支持治疗下的报道范围。这些发现支持了NZW兔模型在急性辐射暴露进一步机械研究和医学对策测试中的实用性。