大剂量重组人粒细胞集落刺激因子对8.0Gy ^60Co γ射线照射小鼠长期存活率及远后效应的影响

目的探索重组人粒细胞集落刺激因子（rhG-CSF）对8.0Gy60Coγ射线照射小鼠长期存活率及远后效应的影响。方法 70只雄性C57BL/6小鼠,随机分为正常对照、照射对照及rhG-CSF大、中、小剂量治疗共5组,除正常对照组外,其他4组均接受8.0Gy60Coγ射线照射。治疗组小鼠于照射后0.5和24h两次分别皮下注射rhG-CSF1000、500和250μg/kg,随时记录各组动物存活率,照射后70、160和300d进行外周血细胞计数分析,300d时检测各组存活小鼠造血和免疫相关指标。结果照射对照组动物照后19d内全部死亡,平均存活时间（12.1±3.0）d;rhG-CSF1000μg/kg治疗组照射后30、100和300d存活率分别为86.7%、86.7%和80.0%,死亡小鼠平均存活时间较照射对照组明显延长（P〈0.01）。照后300d时,rhG-CSF1000μg/kg治疗组的外周血红细胞和血小板计数均与正常对照组没有统计学差异,骨髓混合细胞集落形成单位数量显著低于正常对照组（P〈0.01）;rhG-CSF治疗组的CD4＋/CD8＋比值倒置且250μg/kg剂量组明显低于正常对照组（P〈0.05）;rhG-CSF治疗组造血和免疫器官的组织病理切片结果显示仍然存在不同程度的病变。结论 rhG-CSF1000μg/kg治疗可以显著提高8.0Gy60Coγ射线照射小鼠存活率,但照射后300d造血和免疫系统相关指标尚未完全恢复正常。

Effects of high dose rhG-CSF on the long-term survival rates and delayed effects of mice irradiated by 8. 0 Gy ^60Co γ ray

Objective To investigate the effects of high dose rhG-CSF treatment on the long-term survival rates of mice exposed to 8. 0 Gy ^60Co γ ray. Methods Seventy male C57BL/6 mice were randomly divided into irradiation control group （ n = 15）, normal control group（ n = 10）, high （1000 μg/kg, n = 15 ）,intermediate 4500 μg/kg, n = 15） and low （250 μg/kg, n = 15） dose of rhG-CSF groups. Animals from irradiation control group and treatment groups were exposed to 8. 0 Gy ^60Co γ ray. At 0. 5 and 24 h after irradiation, animals from treatment groups were subcutaneously injected with rhG-CSF at above assigned doses. Survival rates of each group were recorded. Hemograms were observed on day 70,160 and 300 after irradiation. Hematopoietic and immune related indexes were carried out on day 300 after irradiation. Results （ 1 ） All animals from irradiation control group died within 19 days and the average survival time was （ 12.1 ± 3. 0 ） d. On day 30,100 and 300 after irradiation, the survival rates of animals from 1000 μg/kg rhG-CSF group were 86. 7%, 86. 7% and 80. 0% respectively. The mean survival time of animals from 1000 μg/kg rhG-CSF group was significantly longer than that of animals from irradiation control group （ P 〈 0. 01 ）. （2） On day 300 after irradiation, no statistically significant difference was observed on RBC and PLT values between rhG-CSF 1000 μg/kg treatment group and normal control group. （3） CFU-Mix value of bone marrow of high dose rhG-CSF treatment group was significantly lower than that of normal control group （ P 〈 0. 01 ）. （ 4 ） CD4^＋/CD8^＋ ratios of rhG-CSF treatment groups were inverted, but no significant difference with normal control group was observed except for low dose rhG-CSF group which showed inversion and significantly lower of CD4^＋/CD8^＋ ratio than normal control group （P 〈 0. 05）. （5）Hematologic and immunological histopathology still showed varying degrees of lesion in rhG-CSF treatment groups in 8. 0 Gy irradiated mice on day 300. Conelusion High dose rhG-CSF treatment （1000 μg/kg） could markedly improve the survival rate of mice exposed to 8. 0 Gy ^60Co γ ray, but on day 300 after irradiation, hematopoietic and immune related indexes did not show full recovery.