Moqattash S, Lutton J D, Rosenthal G, Abu-Hijleh M F, Abraham N G
Department of Human and Clinical Anatomy, Sultan Qaboos University College of Medicine, Muscat, Oman.
Acta Haematol. 1997;98(2):76-82. doi: 10.1159/000203596.
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.
我们测定了输注人重组血红蛋白1.1（hr-Hb）和促红细胞生成素在正常小鼠及艾滋病小鼠模型（MAIDS小鼠）体内挽救造血活性、使其免受齐多夫定（AZT）抑制作用的能力。在最后4周，给小鼠喂食AZT，并给予不同浓度的hr-Hb和/或促红细胞生成素（Epo）进行治疗，持续8周。测定所有小鼠的血液参数、体重（BW）和红系爆式集落形成单位（BFU-E）。接受AZT治疗的正常小鼠和MAIDS小鼠的血细胞比容（分别下降64%和78.1%）、血红蛋白（分别下降27.2%和45.5%）、体重（分别下降17.5%和35.5%）、白细胞数量（分别下降66.9%和42.1%）、红细胞数量（分别下降65.5%和38%）以及BFU-E数量（分别下降73%和59%）均显著降低，而接受hr-Hb（5 mg/kg体重/天）和/或Epo（2 U/小鼠/天）治疗的接受AZT治疗的正常小鼠和MAIDS小鼠，AZT的细胞毒性得到了显著缓解。这在所有检测的血液指标、BFU-E数量以及治疗小鼠的体重恢复中都很明显。与对照组相比，MAIDS小鼠中BFU-E的恢复率（97%）高于正常小鼠（63%）。hr-Hb产生的反应与联合用药相似，不过在某些血液学参数方面，联合用药的恢复情况稍好一些。更高浓度的hr-Hb（10 - 15 mg）并未使大多数血液指标有更显著的增加。我们的结果表明，输注hr-Hb可减轻正常小鼠和免疫缺陷小鼠体内AZT的毒性，并且hr-Hb在临床上可能有助于预防由各种药物或制剂（如AZT）引起的严重骨髓抑制。
