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首页> 外文期刊>Life sciences >IMPROVEMENT OF ANEMIA IN W/W-V MICE BY RECOMBINANT HUMAN ERYTHROPOIETIN (RHUEPO) MEDIATED THROUGH EPO RECEPTORS WITH LOWERED AFFINITY
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IMPROVEMENT OF ANEMIA IN W/W-V MICE BY RECOMBINANT HUMAN ERYTHROPOIETIN (RHUEPO) MEDIATED THROUGH EPO RECEPTORS WITH LOWERED AFFINITY

机译：重组人促红细胞生成素（RHUEPO）介导的具有低亲和力的EPO受体介导的W / W-V小鼠贫血的改善

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We studied the the effects of recombinant human erythropoietin (rHuEPO) on anemic W/W-v mice which manifested severe anemia accompanied by mutation of the W gene encoding tyrosine kinase type receptor (c-kit gene) of bone marrow hematopoietic cells. Nine-week-old male W/W-v mice or normal littermates (+/+) were used. Since serum EPO concentration in W/W-v mice increased in proportion to severity of anemia, EPO production in the kidneys of these animals was found to be regulated normally. Hematocrit in +/+ mice increased and a maximal response was also obtained with 2,000 IU/kg of rHuEPO. On the other hand, hematocrit in W/W-v mice increased in a dose-responsive manner by administration with 2,000 and 10,000 IU/kg, showing different responses to rHuEPO in these two types of mice. The responsiveness of W/W-v mice to rHuEPO was low in terms of increases in erythroblastic precursor cells (CFU-E), and immature cells in the bone marrow. Scatchard analysis of the specific binding of I-125-rHuEPO against bone marrow cells revealed that the different responsiveness to rHuEPO between W/W-v and +/+ mice may be correlated with differences in affinity of EPO receptor of bone marrow cells in these mice. From these results, a high dose of rHuEPO is capable of improving the anemia in W/W-v mice that had EPO receptors with lowered affinity, indicating the possible effectiveness of rHuEPO in anemic patients with EPO receptor abnormality. [References: 24]
机译：我们研究了重组人促红细胞生成素（rHuEPO）对贫血W / W-v小鼠的影响，该小鼠表现出严重的贫血，伴有骨髓造血细胞编码酪氨酸激酶型受体（c-kit基因）的W基因突变。使用九周龄的雄性W / W-v小鼠或正常同窝仔（+ / +）。由于W / W-v小鼠中的血清EPO浓度与贫血的严重程度成比例地增加，因此发现这些动物肾脏中的EPO产生受到正常调节。 + / +小鼠的血细胞比容增加，并且以2,000 IU / kg的rHuEPO也获得了最大的反应。另一方面，通过以2,000和10,000 IU / kg的剂量给药，W / W-v小鼠的血细胞比容以剂量响应方式增加，在这两种类型的小鼠中显示出对rHuEPO的不同反应。 W / W-v小鼠对rHuEPO的反应性低，这是由于促红细胞前体细胞（CFU-E）和骨髓中未成熟细胞的增加所致。对I-125-rHuEPO对骨髓细胞的特异性结合的Scatchard分析显示，W / W-v和+ / +小鼠之间对rHuEPO的不同反应性可能与这些小鼠中骨髓细胞EPO受体亲和力的差异有关。根据这些结果，高剂量的rHuEPO能够改善具有EPO受体的亲和力降低的W / W-v小鼠的贫血，表明rHuEPO在具有EPO受体异常的贫血患者中可能有效。 [参考：24]

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