Effects of recombinant hematopoietins on blood-loss anemia in mice.
Effects of recombinant hematopoietins on blood-loss anemia in mice.
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发表时间：
2005
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通讯作者：
Kevin B. Jones;David W. Anderson;G. Longmore
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作者：
Kevin B. Jones;David W. Anderson;G. Longmore
使用重组人促红细胞生成素（rhEPO）治疗骨科手术失血引起的术前贫血已成为常规做法。使用rhEPO来帮助管理择期手术或主要骨科创伤的意外失血受到外源性rhEPO可实现的红细胞生成速率和体积的限制。红细胞生成的速率和体积可能受到对EPO有反应的可用细胞群的限制。已知影响这些早期造血祖细胞的细胞因子可能增强rhEPO的作用。在这项研究中，小鼠通过损失约三分之一的总血量而贫血。对照组仅接受铁补充剂。三个实验组的小鼠接受三次rhEPO注射。其中两组还接受重组鼠干细胞因子（rmSCF）或重组鼠白细胞介素-3（rmIL-3）。两者都是在rhEPO之前和与rhEPO联合使用。在基线、rhEPO给药前开始rmSCF和rmIL-3后以及rhEPO给药后三个时间点处死动物进行外周血检测。另外，收获骨髓并培养以测定用rmIL-3或rmSCF处理后以及进一步用rhEPO处理后红系祖细胞的浓度。在接受额外细胞因子的组中，给予rhEPO后第一个测量点的血细胞比容显着较高。对照组和仅rhEPO组在该早期时间点没有差异。在接受额外细胞因子的组中，红细胞生成的最大速率也升高。与所有其他组相比，接受SCF的小鼠的骨髓具有显著增加的红系祖细胞数量。EPO反应细胞的数量依赖于不受缺氧控制的细胞因子，是失血性贫血恢复期间对rhEPO反应的主要限速和容量限制因素。早期作用的细胞因子的管理有可能增加外源性刺激的红细胞生成的速度和体积。
Use of recombinant human erythropoietin (rhEPO) for treatment of pre-operative anemia in anticipation of orthopaedic surgical blood loss has become a routine practice. Use of rhEPO to help manage unanticipated blood loss from elective surgery or major orthopaedic trauma is limited by the rate and volume of erythropoiesis that is achievable with exogenously administered rhEPO. The rate and volume of erythropoiesis may be limited by the available population of cells responsive to EPO. Cytokines known to affect these early hematopoietic progenitors may potentiate the effects of rhEPO. In this study, mice were rendered anemic by loss of approximately one-third of their total blood volume. A control group received only iron supplementation. Mice in three experimental groups received three injections of rhEPO. Two of these groups also received either recombinant murine stem cell factor (rmSCF) or recombinant murine interleukin-3 (rmIL-3). Both were before and in conjunction with rhEPO. Animals were sacrificed for peripheral blood testing at baseline, after initiation of rmSCF and rmIL-3 prior to rhEPO administration, and at three time points after dosing of rhEPO. Additionally, the bone marrow was harvested and cultured to determine the concentration of erythroid progenitors after treatment with rmIL-3 or rmSCF, and after further treatment with rhEPO. Hematocrits were significantly higher in the first measurement point after administration of rhEPO in the groups receiving additional cytokines. The control and rhEPO-only groups were not different at this early time point. The maximal rate of erythropoiesis was also elevated in the groups receiving additional cytokines. The bone marrow of mice receiving SCF had a dramatically increased number of erythroid progenitors compared to all other groups. The population of EPO-responsive cells, dependent on cytokines not controlled by hypoxia, is a major rate-limiting and volume-limiting factor in the response to rhEPO during recovery from blood-loss anemia. Administration of earlier-acting cytokines has the potential to increase the rate and volume of exogenously stimulated erythropoiesis.