中华放射医学与防护杂志

罗庆良,Neelis KJ,Wagemaker G.重组人血小板生长因子和重组人粒细胞集落刺激因子对急性放射病猴的治疗作用[J].中华放射医学与防护杂志,1999,19(1):34-38

重组人血小板生长因子和重组人粒细胞集落刺激因子对急性放射病猴的治疗作用

Therapeutic effect of TPO and G CSF on acute radiation sickness of monkeys

投稿时间：1998-08-12 修订日期：1998-11-12

DOI：

英文关键词:Thrombopoietin Granulocyte colony stimulating factor Acute radiation sickness Hematopoietic growth factor

基金项目:

作者	单位
罗庆良	100850 北京放射医学研究所
Neelis KJ	Erasmus University, 3000DR Rotterdam, The Netherlands.
Wagemaker G	Erasmus University, 3000DR Rotterdam, The Netherlands.

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中文摘要:

目的本文作者观察了rhTPO和rhG-CSF对急性放射病猴的治疗效果, 旨在为造血因子的临床应用提供理论依据。方法正常雄性成年猕猴20只, 随机分为rhTPO10μg·kg^-1·d^-1、G-CSF10μg·kg^-1·d^-1、TPO+G-CSF和照射对照4组。动物照射的吸收剂量为5.0Gy(300kVX射线, 吸收剂量率为0.20～0.22Gy/min);给药方法均为皮下注射, 连续给药21天。结果 ①外周血小板：照后第7天TPO治疗组开始下降, 第10天达最低值(45%, 以照前值为100%, 下同), 第14天达照前值水平, 第21天达最高值(311%), 第30天仍为263%.G-CSF治疗组第9天仅为照前值的10%, 照后第30天接近照前水平(92%).对照组照后第7天开始迅速下降, 第16天达最低值(9%), 仅为TPO治疗组的5.9%(P<0.01), 第30天(80%)仍未恢复到照前值水平。②外周血网织红细胞百分比：4组动物照后均迅速下降, TPO治疗组于照后第8天达最低值(11%), 低于照前值50%的时间为8天, 第12天开始迅速回升, 第20天达最高值(402%).G-CSF治疗组及对照组动物下降程度更为迅速, 第9天分别为照前值的7%和9%, 低于照前值孙%的时m均长达16大, 照石第29和27天达最高值(分别为352%和408%)o③外周血白细胞：G-CSF治疗组于照后第7天迅速降至4.9%, 第20夭回升至照前水平, 停药后又降至89%~74%oTPO治疗组及对照组变化趋势一致, 低于SO%照前值的时间均为23天, 照后第30天仍未恢复至照前水平(分别为65.3%和46.6%)0④病程极期对照组动物均接受了2--3次血小板悬液或全血输注, 而TPO或G-CSF治疗组动物均不需要精血或输血小板悬液。结论重组人TPO可明显促进S.OGy照射猴外周血小板和网织红细胞的恢复。G-CSF可明显地促进照射动物外周血白细胞的恢复。这些造血因子为事故性急性放射病等造血功能障碍性疾病的临床治疗显示了良好的前景。

英文摘要:

Objective This report describes the therapeutic effects of recombinant human thrombopoietin(rhTPO) and recombinant human granulocyte colony stimulating factor(rhG-CSF) on acute radiation sickness in monkeys.Methods rhTPO(10μg·kg ^-1 ·d^-1 ,sc,on days 1-21 after TBI)or/and rhG-CSF(5μg·kg^-1 ·d^-1 ,sc,on days 1-21 after TBI) were administered to rhesus monkeys with 5.0Gy X-irradiation.Results rhTPO promoted platelet and reticulocyte recovery,resulting in less profound nadirs and a rapid recovery to normal levels.Platelet transfusions were not required in contrast to controls,while hemoglobin levels stabilized rapidly.TPO treatment did not influence neutrophil counts, rhG-CSF stimulated neutrophil regeneration and had no effect on platelet levels.Simultaneous administration of rhTPO and rhG GSF were as effective as rhTPO alone in preventing thrombopenia,although the platelet level did not rise to the supranormal level seen with TPO alone. The neutropils were greatly augmented in number,compared to G-CSF treatment alone,resulting in a less profound nadir and much earlier recovery,which was similarly observed for monocytes,CD¹¹ b⁺,CD⁺₁₆ and CD⁺₅₆ cell reconstitution. Conclusion These data show that rhTPO and rhG-GSF are potent stimulators of hematopoiesis in monkeys with radiation sickness.

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