重组人粒细胞集落刺激因子融合蛋白对急性放射病小鼠的治疗作用

Therapeutic effect of recombinant human serum albumin-granulocyte colony-stimulating factor fusion protein on mice with acute radiation sickness

目的研究重组人血清白蛋白-粒细胞集落刺激因子融合蛋白(GW003)对急性辐射损伤小鼠的治疗作用。方法 80只BALB/c小鼠用60Coγ射线一次全身照射5.0 Gy后随机分为照射对照,GW003 1、3和9 mg/kg 4组,照射后1 h和7 d分别皮下注射生理盐水,GW003 1、3和9 mg/kg。照前1 d和照后30 d内隔日一次检测外周血细胞,照射后30 d处死小鼠取胸骨行组织病理学观察。结果 60Coγ射线5.0 Gy照射后小鼠外周血白细胞、中性粒细胞、淋巴细胞和单核细胞数急剧下降,其中1和3 mg/kg GW003组白细胞和中性粒细胞减少持续时间较照射对照组显著缩短,开始恢复时间提前,白细胞最低值明显升高。GW003 9 mg/kg组上述指标与照射对照组相比有所改善,但无显著差异。3 mg/kg GW003组小鼠单核细胞数于照射后9～13 d明显高于照射对照组。各组间外周血淋巴细胞、血小板及红细胞数无明显差异。胸骨病理组织切片显示照射后30 d各组活存小鼠骨髓造血均十分活跃。结论 GW003对60Coγ射线5.0 Gy照射所致急性放射病小鼠有明显的治疗作用。

Objective To investigate the therapeutic effect of recombinant human albumin-granulocyte colony-stimulating factor fusion protein（GW003） on mice with acute radiation injury.Methods Eighty BALB/c mice were total body irradiated with 5.0 Gy 60Co γ-ray and randomly assigned to vehicle,GW003 1,3 and 9 mg/kg groups.The mice were administrated subcutaneously with 0.9% sodium chloride,GW003 1,3and 9 mg/kg,respectively.To evaluate the therapeutic effect,peripheral blood（PB） was obtained to assay complete blood and differential cell counts every two days.Thirty days post irradiation mice were anesthetized with pentobarbital and sternums were obtained for histopathologic evaluation.Results The quantity of leukocytes,neutrophils,lymphocytes and monocytes of PB was decreased obviously after irradiation.In GW003 1 and 3 mg/kg groups,the leukocytopenia and neutrocytopenia were shortened and quicker to recover while the nadir of leukocytes was elevated.During 9-13 d post irradiation monocytes count among GW003 3.0 mg/kg injection mice was higher than that from vehicle mice.No significant difference was observed among the four groups in lymphocytes,erythrocytes and platelets.Sternum pathological section indicated that the hematogenesis function of marrow was active in the live mice of the four groups.Conclusion GW003 has obvious therapeutic effect on acute radiation injury of mice exposed to 5.0 Gy 60Co γ-ray.