中华放射医学与防护杂志

李明,欧红玲,邢爽,等.细胞因子治疗4.5Gyγ射线照射比格犬造血损伤的机制初探[J].中华放射医学与防护杂志,2010,30(3):239-242.LI Ming,OU Hong-ling,XING Shuang,et al.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[J].Chin J Radiol Med Prot,2010,30(3):239-242

细胞因子治疗4.5Gyγ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

投稿时间：2009-12-24

DOI：10.3760/cma.j.issn.0254-5098.2010.03.002

中文关键词: 急性放射病细胞因子造血损伤 CD34 细胞细胞周期细胞凋亡比格犬

英文关键词:Acute radiation sickness Cytokines Hematopoietic injuries CD34 cells Cell cycle Apoptosis Beagles

基金项目:国防科工委"十一五"核科学基础研究重点项目(A3620060130)

作者	单位	E-mail
李明	100850 北京, 军事医学科学院放射与辐射医学研究所
欧红玲	第二炮兵总医院
邢爽	100850 北京, 军事医学科学院放射与辐射医学研究所
黄海潇	100850 北京, 军事医学科学院放射与辐射医学研究所
熊国林	100850 北京, 军事医学科学院放射与辐射医学研究所
谢玲	100850 北京, 军事医学科学院放射与辐射医学研究所
赵燕芳	100850 北京, 军事医学科学院放射与辐射医学研究所
赵振虎	100850 北京, 军事医学科学院放射与辐射医学研究所
王宁	100850 北京, 军事医学科学院放射与辐射医学研究所
王金香	苏州大学医学部
缪竞诚	苏州大学医学部
朱南康	苏州大学医学部
罗庆良	100850 北京, 军事医学科学院放射与辐射医学研究所
从玉文	100850 北京, 军事医学科学院放射与辐射医学研究所
张学光	苏州大学医学部	xgzh@ yahoo. com. cn

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中文摘要:

目的探讨多种细胞因子配伍应用治疗4.5 Gy γ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 Gy ⁶⁰Co γ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 Gy γ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。

英文摘要:

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 Gy ⁶⁰Co γ-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 Gy ⁶⁰Co 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, rhIL-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 ⁶⁰Co 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 G₀/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 hematopoietic injuries induced by irradiation.

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