Effect of blood substitute, recombinant hemoglobin, on in vivo hematopoietic recovery from AZT toxicity.
Effect of blood substitute, recombinant hemoglobin, on in vivo hematopoietic recovery from AZT toxicity.
复制标题
血液替代品、重组血红蛋白对 AZT 毒性体内造血恢复的影响。
DOI：
10.1159/000203596
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发表时间：
1997
影响因子：
2.4
通讯作者：
Abraham,NG
中科院分区：
文献类型：
--
作者：
Moqattash,S;Lutton,JD;Rosenthal,G;Abu-Hijleh,MF;Abraham,NG
我们确定了在体内输注的人重组血红蛋白1.1（hr-Hb）和促红细胞生成素的能力，以拯救造血活动的抑制作用的AZT在正常和艾滋病（MAIDS）小鼠的小鼠模型。在最后4周通过给予不同浓度的hr-Hb和/或促红细胞生成素（Epo），给小鼠喂食AZT 8周，同时进行或不进行治疗。测定所有小鼠的血液参数、体重（BW）和红系爆发形成单位（BFU-E）。AZT治疗的正常和MAIDS小鼠显示血细胞比容显著降低，（64和78.1%），血红蛋白（27.2%和45.5%），体重（17.5%和35.5%），白色人数（66.9%和42.1%）和红细胞（65.5%和38%），以及BFU-E的数量（73和59%），而接受hr-Hb（5 mg/kg BW/天）和/或Epo（2 U/小鼠/天）的AZT治疗的正常和MAIDS小鼠显示AZT细胞毒性显著减轻。这通过检查的所有血液指数、BFU-E数量和给药小鼠的BW的恢复而得到证实。与对照组相比，MAIDS中的BFU-E回收率（97%）高于正常小鼠（63%）。hr-Hb产生了与组合相似的反应，但是在一些血液学参数中，后者的恢复略好。较高浓度的hr-Hb（10-15 mg）不会导致大多数血液指标的显著增加。我们的研究结果表明，输注hr-Hb可以减轻AZT在正常和免疫缺陷小鼠的毒性，hr-Hb可能是临床上有用的，在防止严重的骨髓抑制所带来的各种药物或代理，如AZT。
We determined the in vivo ability of infused human recombinant hemoglobin 1.1 (hr-Hb) and erythropoietin to rescue the hematopoietic activity from the suppressive effects of AZT in normal and in a murine model of AIDS (MAIDS) mice. Mice were fed with AZT for 8 weeks with or without treatment in the last 4 weeks by administering various concentrations of hr-Hb and/or erythropoietin (Epo). Blood parameters, body weight (BW) and erythroid burst-forming units (BFU-E) for all mice were determined. AZT-treated normal and MAIDS mice showed a significant decrease in hematocrit (64 and 78.1%), hemoglobin (27.2 and 45.5%), BW (17.5 and 35.5%), number of white (66.9 and 42.1 %) and red blood cells (65.5 and 38%), and the number of BFU-E (73 and 59%), whereas the AZT-treated normal and MAIDS mice that received hr-Hb (5 mg/kg BW/day) and/or Epo (2 U/mouse/day) showed significant alleviation of AZT cytotoxicity. This was evident by the recovery in all blood indices examined, the number of BFU-E and the BW of mice treated. BFU-E recovery in MAIDS (97%) was greater than that in normal mice (63%) as compared to their controls. hr-Hb produced a similar response as the combination, however recovery was slightly better with the latter in some hematological parameters. Higher concentrations of hr-Hb (10-15 mg) did not result in a more significant increase in most blood indices. Our results indicate that infusion with hr-Hb can alleviate AZT toxicity in normal and in immunodeficient mice, and that hr-Hb may be clinically useful in preventing severe bone marrow depression brought about by various drugs or agents such as AZT.