不同结构粒细胞集落刺激因子对3.0Gy(60)Coγ射线照射恒河猴的治疗作用

摘要

目的 本研究旨在观察不同结构重组人粒细胞集落刺激因子(rhG-CSF)吉粒芬和GW003对急性放射病猴的治疗作用.方法 18只成年恒河猴用(60)Coγ射线全身双侧一次均匀照射3.0Gy,实验分为照射对照、吉粒芬(rhG-CSF)和GW003治疗共3组,每组6只动物.吉粒芬治疗组动物于照射后0～13 d给予吉粒芬5μg/kg,每天一次皮下注射.GW003治疗组动物分别于照射后0和7d共两次给予GW003 150μg/kg皮下注射.观察照射后动物一般体征、外周血细胞计数、骨髓细胞集落形成能力,照射后60d胸骨、脾脏、淋巴结等造血免疫组织的组织病理学改变.结果 与照射对照组相比,GW003150μg1kg 1次/周连续两周给药方案可以明显升高照射动物外周血白细胞、中性粒细胞数最低值,促进骨髓造血功能恢复,缩短对症治疗中抗生素和止血药应用时间,减少输血次数,从而简化综合对症治疗措施.吉粒芬治疗组上述指标较照射对照组有明显改善,但外周血细胞和中性粒细胞数最低持续时间明显长于GW003治疗组(P<0.05).结论 GW003150μg/kg对3.0Gy(60)γ射线照射恒河猴有明显的治疗作用,该给药方案比吉粒芬5μg/kg每天一次连续14d皮下注射给药方案更具优势.%Objective To investigate the therapeutic effect of granulocyte-eolony stimulating factors (G-CSF) with different structures on Rhesus monkeys irradiated by 3.0 Gy 60Co γ ray. Methods Eighteen 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 (n=6), JiLiFen(R) (rhG-CSF) control group (n=6) or GW003 (long-term G-CSF) group (n=6). Monkeys in JiLiFen(R) group were subcutaneously injected with rhG-CSF at a dose of 5 μg/kg from day 0 to day 13 and those in GW003 group were subcutaneously injected with GW003 at a dose of 150 μg/kg at day 0 and day 7, respectively. General signs and peripheral blood cell counts were monitered and histopathologic changes in hematological and immunological tissues were evaluated during 60 days following irradiation.Results Weekly administration of GW003(150 μg/kg) elevated the nadirs of leucocytes and neutrophils in peripheral blood of monkeys exposed to 3.0 Gy γ ray, promoted hematopoiesis recovery, shortened duration of supportive care, reduced blood transfusion frequency, and simplified supportive care measurements. Conclusion Administration of GW003 (150 μg/kg) weekly has proved to have therapeutic effects on Rhesus monkeys irradiated by 3.0 Gy 60Co γ ray. The dosage regimen of GW003 is superior to daily injection of JiLiFen(R) 5μg/kg for 14 consecutive days.