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尿毒症性红细胞生成抑制剂:重组人促红细胞生成素治疗期间的一项研究

Uremic inhibitors of erythropoiesis: a study during treatment with recombinant human erythropoietin.

作者信息

Brunati C, Cappellini M D, De Feo T, Guastoni C, Ballerini L, Busnach G, Civati G, Fiorelli G, Minetti L

机构信息

Divisione di Nefrologia e Dialisi, Niguarda Cà Granda, Milan, Italy.

出版信息

Am J Nephrol. 1992;12(1-2):9-13. doi: 10.1159/000168410.

DOI:10.1159/000168410
PMID:1415372
Abstract

The effects of increasing amounts of uremic sera (US) on the growth of erythroid progenitor cells [burst-forming unit erythroid (BFU-E)] collected from peripheral blood of normal subjects were evaluated to assess the potential role of uremic inhibitors of erythropoiesis during a treatment with recombinant human erythropoietin (r-HuEpo). US were collected from 8 patients on regular dialysis with marked anemia (Hb 6 +/- 0.5 g%) before and after a treatment with high doses of r-HuEpo (from 300 to 525 U/kg/week). Standard cultures for BFU-E were performed in alpha-metylcellulose with fetal calf serum (FCS) and 4 U/ml of r-HuEpo (Cilag, Ortho). In successive cultures, US were added at increasing amounts to the standard culture in order to assess a possible inhibitory effect on BFU-E growth. Finally, in order to assess a possible lack of stimulatory factors, we partially substituted FCS with US. The addition of US collected either before or after therapy with r-HuEpo to the standard culture had no effect on the growth of BFU-E. Vice versa, the number of cultured BFU-E decreased when FCS was partially substituted with US collected before r-HuEpo. This effect was not evident when FCS was partially substituted with US collected after r-HuEpo. No significant differences were recorded in the tested sera collected before and after therapy considering erythropoietin levels and amino acid levels. We hypothesized that some other factors with erythropoietic stimulatory activity (burst-promoting activity?) may be deficient in uremic patients with marked anemia and can be induced during therapy with r-HuEpo.

摘要

评估了尿毒症血清(US)量增加对从正常受试者外周血中采集的红系祖细胞[红系爆式集落形成单位(BFU-E)]生长的影响,以评估在重组人促红细胞生成素(r-HuEpo)治疗期间尿毒症促红细胞生成抑制剂的潜在作用。US取自8例重度贫血(血红蛋白6±0.5g%)且正在进行规律透析的患者,这些患者在接受高剂量r-HuEpo(300至525U/kg/周)治疗前后采集。BFU-E的标准培养在含有胎牛血清(FCS)和4U/ml r-HuEpo(Cilag,Ortho)的α-甲基纤维素中进行。在连续培养中,将逐渐增加量的US添加到标准培养物中,以评估对BFU-E生长的可能抑制作用。最后,为了评估可能缺乏刺激因子的情况,我们用US部分替代FCS。将r-HuEpo治疗前后采集的US添加到标准培养物中对BFU-E的生长没有影响。反之,当用r-HuEpo治疗前采集的US部分替代FCS时,培养的BFU-E数量减少。当用r-HuEpo治疗后采集的US部分替代FCS时,这种效应不明显。考虑到促红细胞生成素水平和氨基酸水平,治疗前后采集的受试血清中未记录到显著差异。我们推测,一些具有促红细胞生成刺激活性(爆式促进活性?)的其他因子在重度贫血的尿毒症患者中可能缺乏,并且在r-HuEpo治疗期间可被诱导产生。

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