大剂量粒细胞集落刺激因子对2.3Gy中子γ射线混合照射比格犬存活和造血重建的影响(英文)

High Dose Granulocyte Colony-Stimulating Factor Enhances Survival and Hematopoietic Reconstruction in Canines Irradiated by 2.3 Gy Mixed Fission Neutron and Gamma Ray

本研究旨在观察大剂量重组人粒细胞集落刺激因子(rhG-CSF)对中子-γ射线混合照射比格犬的治疗作用。13只比格犬用90%裂变中子(n∶γ=10.6∶1)单侧一次照射2.3 Gy。实验分为照射对照(n=4)、对症治疗(n=5)和rhG-CSF治疗(n=4)3组。rhG-CSF治疗组照射后0.5和24小时2次皮下注射rhG-CSF 200μg/kg。结果表明,2.3 Gy 90%裂变中子照射可致重度骨髓型急性放射病,照射后50天3组动物分别活存1/4、3/5和4/4;rhG-CSF给药可使动物存活率由对症治疗组的60%提高至100%。与对症治疗组比较,照射后24小时内2次给予rhG-CSF可缩短中性粒细胞减少持续时间,提高中性粒细胞最低值,并促进其恢复。rhG-CSF治疗组照射后3天外周血有核细胞形成集落数量(CFU-GM、CFU-E和BFU-E)明显增加,为对症治疗组的2-5倍。照射后50天,胸骨病理切片检查结果显示,rhG-CSF治疗动物造血全部恢复正常,而对症治疗组动物仍然存在造血细胞数量严重减少。结论:照射后早期大剂量rhG-CSF 2次皮下注射联合对症治疗可明显促进2.3 Gy裂变中子-γ射线混合照射比格犬造血功能恢复,提高其存活。

This study was purposed to evaluate the effects of recombinant human granulocyte colony-stimulating factor （rhG-CSF） on hematopoietic reconstruction and survival in beagles exposed to mixed fission neutron and γ-ray. 13 beagles were unilaterally exposed to single dose of 2.3 Gy 90% neutrons. The experiments were divided into 3 groups： irradiation control group （ no any treatment, n = 4 ）, supportive care group （ n = 5 ） and rhG-CSF plus supportive care group （n =4, abbreviated as rhG-CSF group） in which the beagles were subcutaneously injected with 200μg/kg of rhG-CSF early at half an hour and 24 hours post-irradiation respectively. The results showed that 2.3 Gy 90% neutron irradiation induced a severe acute radiation sickness of bone marrow type. The administration of rhG-CSF increased the survival rate from 60% in supportive care group to 100%. Twice injection of rhG-CSF in the first 24 hours reduced duration of neutropenia, enhanced neutrophil nadir and promoted neutrophil recovery when compared with control cohort ad- ministered clinical support. The number of colony-forming cells （CFU-GM, CFU-E, and BFU-E） in peripheral blood of rhG-CSF treated canines increased 2- to 5-fold relative to those of the supportive care group on day 3. All canines treated with rhG-CSF achieved hematopoietic reconstruction as evidenced by the pathological section of sternum while severe shortage of hemopoietic cells remained in the cohorts given supportive care alone. It is concluded that the combination of supportive care and high-dose rhG-CSF can accelerate hematopoietic recovery and enhance survival of dogs exposed to 2. 3 Gy mixed neutron and gamma ray.