细胞因子治疗4.5 Gyγ射线照射比格犬造血损伤的机制初探  

Studies on mechanism of treatment of granulocyte colony-stimulating factor,recombinant human interleukin-11 and recombinant human interleukin-2 on hematopoietic injuries induced by 4.5 Gy γ-rays irradiation in beagles

作　　者：李明[1] 欧红玲[2] 邢爽[1] 黄海潇[1] 熊国林[1] 谢玲[1] 赵燕芳[1] 赵振虎[1] 王宁[1] 王金香[3] 缪竞诚[3] 朱南康[3] 罗庆良[1] 从玉文[1] 张学光[3] 

机构地区：[1]军事医学科学院放射与辐射医学研究所,北京100850 [2]第二炮兵总医院 [3]苏州大学医学部

出　　处：《中华放射医学与防护杂志》2010年第3期239-242,共4页Chinese Journal of Radiological Medicine and Protection

基　　金：国防科工委“十一五”核科学基础研究重点项目（A3620060130）

摘　　要：目的 探讨多种细胞因子配伍应用治疗4.5 Gyγ射线照射比格犬造血系统损伤的作用及可能机制.方法 16只比格犬均给予4.5 Gy60Coγ射线全身照射,随机分为照射对照、综合对症和细胞因子3组.细胞因子组在综合对症支持治疗的基础上应用rhG-CSF、rhIL-11和rhIL-2联合治疗,采用流式细胞术检测外周血中CD34＋细胞含量、有核细胞周期及凋亡比例.结果 4.5 Gyγ射线照射犬外周血中CD34＋细胞含量在照射后1 d明显下降（照射对照组和综合对症组分别为照前值的61.3%和52.1%）,G0/G1期有核细胞比例增加（分别为99.27%和99.49%）,且凋亡率（分别为26.93%和21.29%）和坏死率（分别为3.27%和4.14%）明显升高（与照前值比较,P〈0.05）;而经过细胞因子治疗后,外周血中CD34＋细胞含量在照射后1 d即明显升高（为照前值的135.6%）,G0/G1期有核细胞比例（99.71%）进一步增加,其凋亡率（5.66%）和坏死率（1.60%）明显低于照射对照和综合对症组.结论 本研究的细胞因子组合可能通过动员骨髓中CD34＋细胞到外周血,使细胞周期阻滞在G0/G1期,减少细胞凋亡,从而促进极重度骨髓型急性放射病犬造血功能的恢复.Objective To investigate the mechanism of treatment of granulocyte colony-stimulating factor（rhG-CSF）,recombinant human interleukin-11（rhIL-11）and recombinant human interleukin-2 （rhIL-2）on hematopoietic injuries induced by 4.5 Gy60 Coγ-ray irradiation in beagles,and to provide experimental evidence for the clinical treatment of extremely severe myeloid acute radiation sickness （ARS）.Methods Sixteen beagle dogs were given 4.5 Gy60 Co γ-ray total body irradiation（TBI）,then randomly assigned into irradiation control group,supportive care group or cytokines＋supportive care （abbreviated as cytokines）group.In addition to supportive care,rhG-CSF,rhlL-11 and rhIL-2 were administered subcutaneously to treat dogs in cytokines group.The percentage of CD34＋cells,cell cycle and apoptosis of nucleated cells in peripheral blood were examined by Flow cytometry.Results After 4.5 Gy 60 Co γ-ray irradiation,the CD34＋cells in peripheral blood declined obviously（61.3%and 52.1% of baseline for irradiation control and supportive care group separately）.The cell proportion of nucleated cells in Go/G1 phase was increased notably（99.27% and 99.49% respectively）.The rate of apoptosis（26.93% and 21.29% separately）and necrosis（3.27% and 4.14%,respectively）of nucleated cells were elevated significantly when compared with values before irradiation（P〈0.05） 1 d post irradiation.When beagles were treated with cytokines and supportive care,the CD34＋cells in peripheral blood were markedly increased（135.6% of baseline）.The effect of G0/G1 phase blockage of nucleated cells became more serious（99.71%）.The rate of apoptosis（5.66%）and necrosis（1.60%）of nucleated cells were significantly lower than that of irradiation control and supportive care groups 1 d after exposure.Conclusions Cytokines maybe mobilize CD34＋cells in bone marrow to peripheral blood,indce cell cycle block at G0/G1 phase and reduce apoptosis,and eventually cure hematopoieticinjuries induced by irradiation.

关 键 词：急性放射病 细胞因子 造血损伤 ED34+细胞 细胞周期 细胞凋亡 比格犬 

分 类 号：R818[医药卫生—放射医学]