Biljanović-Paunović L, Djukanović L, Lezaić V, Stojanović N, Marisavljević D, Pavlović-Kentera V
Institute for Medical Research, POBox 721, 11000 Belgrade, Yugoslavia.
Eur J Med Res. 1998 Dec 16;3(12):564-70.
Studies of hemopoietic progenitors and precursors in bone marrow before and after two months of recombinant human erythropoietin (rhEpo) therapy in 12 patients with uremic anemia are the subject of this investigation caried out in order to have a better insight into the effect of Epo in vivo. Eight patients were on hemodialysis and four others were predialysis patients with chronic renal failure. The starting dose of rhEpo was 30-50 U/kg bw and was increased by 50 percent every four weeks. The mean hemoglobin values rose from 6.08 +/- 1.03 to 9.8 +/- 1.98 g/dl at the time of study. The number of bone marrow derived erythroid colonies, both early (BFU-E) and late (CFU-E) were found to be higher than subnormal values, found before the therapy. The percentage of erythroid progenitors in cell cycle increased to higher than normal values for BFU-E and to normal values for CFU-E. At the same time granulocytic progenitors (CFU-GM) decreased to the range of normal values (67.3 per 10 superset5 cells). Slightly increased Epo levels (approx. 30mU/ml) during the replacement therapy were optimal for correction of anemia. The rhEpo therapy induced an increase of percentage of erythroblasts and the decrease of myeloid to erythroid ratio (M/E) in the bone marrow. Only in predialysis patients in whom the target hemoglobin values were achieved by rhEpo therapy at the time of the study the percentage of erythroblasts in the bone marrow increased to normal values. Increase of erythroblasts in bone marrow in patients under two months of substitutive therapy with rhEpo with the increase of both, early and late erythroid progenitors we have observed, is significant indicating the stimulative effect of rhEpo on all subsets of erythropoiesis leading to normalization of erythropoiesis at all levels. No stimulative effect of rhEpo replacement therapy on granulopoiesis was observed.
本研究旨在更好地了解促红细胞生成素（Epo）在体内的作用，对12例尿毒症贫血患者进行了重组人促红细胞生成素（rhEpo）治疗两个月前后骨髓中造血祖细胞和前体细胞的研究。8例患者接受血液透析，另外4例为慢性肾衰竭的透析前患者。rhEpo的起始剂量为30 - 50 U/kg体重，每四周增加50%。研究时平均血红蛋白值从6.08±1.03升至9.8±1.98 g/dl。发现骨髓来源的红系集落数量，包括早期（BFU - E）和晚期（CFU - E）均高于治疗前的低于正常水平的值。细胞周期中红系祖细胞的百分比，BFU - E增加至高于正常水平，CFU - E增加至正常水平。同时，粒系祖细胞（CFU - GM）降至正常范围（每10⁵个细胞67.3个）。替代治疗期间Epo水平略有升高（约30mU/ml）最有利于纠正贫血。rhEpo治疗导致骨髓中早幼红细胞百分比增加，髓红比（M/E）降低。仅在研究时通过rhEpo治疗达到目标血红蛋白值的透析前患者中，骨髓中早幼红细胞百分比增加至正常水平。我们观察到，在接受rhEpo替代治疗两个月的患者中，随着早期和晚期红系祖细胞数量的增加，骨髓中早幼红细胞增加，这表明rhEpo对红细胞生成的所有亚群均有刺激作用，导致各级红细胞生成正常化。未观察到rhEpo替代治疗对粒细胞生成有刺激作用。
