GW003对恒河猴急性辐射损伤的治疗作用

目的本研究旨在观察不同剂量重组人血清白蛋白-粒细胞集落刺激因子融合蛋白（GW003）对急性放射病恒河猴的治疗作用。方法 28只成年恒河猴分为正常对照组、照射对照组及GW003 50、150和450μg/kg治疗组共5组,后4组动物（每组6只）用60Coγ射线全身双侧一次照射3.0 Gy。GW003治疗组动物分别于照射后0和7 d皮下注射GW003 50、150和450μg/kg,所有照射动物均给予对症治疗。观察照射动物一般状况、体征、外周血细胞计数、外周血和骨髓细胞集落培养及病理组织学检查结果。结果不同剂量GW003皮下注射给药能明显升高3.0 Gy照射猴外周血白细胞、中性粒细胞和造血祖细胞数,其中GW003 150和450μg/kg剂量组提高外周血白细胞、中性粒细胞、血小板和血红蛋白最低值,缩短细胞减少持续时间的作用显著,明显加速骨髓造血功能恢复,减少输血次数。结论 GW003 150μg/kg可明显促进急性辐射损伤猴造血功能恢复,对中度骨髓型急性放射病有明显的治疗作用。

Therapeutic effect of GW003 on rhesus monkeys with acute radiation injuries

Objective To investigate the therapeutic effects of different doses of recombinant human albumin-granulocyte colony-stimulating factor fusion protein（GW003） on acute radiation injury rhesus monkeys irradiated by 3.0 Gy 60Co γ ray.Methods Twenty-four adult rhesus monkeys were exposed to a bilateral irradiation at a single dose of 3.0 Gy 60Co γ-ray and randomly assigned into irradiation control group,and GW003 50,150 and 450 μg/kg groups.The other four monkeys were used as normal group with a detection index.Monkeys in GW003 groups were subcutaneously injected with GW003 at a dose of 50,150 and 450 μg/kg at day 0 and 7 after irradiation,respectively,and those in irradiation control group were subcutaneously injected with vehicle.General signs and manifestation,peripheral blood（PB）cell counts,PB and bone marrow cell colony formation units were monitored and histopathologic changes in hematological and immunological tissues were evaluated during sixty days following irradiation.Results Weekly administration of GW003（50-450 μg/kg） could significantly increase the counts of leukocytes,neutrophils and hematopoietic progenitor cells in peripheral blood of rhesus monkeys exposed to 3.0 Gy 60Co γ-ray.GW003 150 and 450 μg/kg elevated the nadirs of leukocytes,neutrophils,platelets and hemoglobin,and shortened duration of pancytopenia,accelerated hematogenesis recovery,reduced blood transfusion frequency,and simplified supportive care measurements.Conclusion Weekly administration of GW003 150 μg/kg has proved therapeutic effects on acute radiation injured rhesus monkeys irradiated by 3.0 Gy 60Co γ-ray.