促红细胞生成素对早产儿外周血循环中造血祖细胞的作用

Effects of erythropoietin on circulating hemotopoietic progenitor cells in premature infants

目的研究促红细胞生成素（erythropoietin，EPO）治疗早产儿贫血的安全性及有效性，并对其治疗早产儿贫血的内在机制进行探讨。方法对24例贫血早产儿进行随机对照的前瞻性研究，治疗组和对照组各12例。治疗组除采用对照组的常规疗法外，另给予EPO250U／（kg·次），3次／周，皮下注射，共4周。EPO治疗前及治疗2周时应用半固体培养的方法分别对两组外周血中各系造血祖细胞形成的集落数进行比较分析，并对治疗期间的白细胞总数、中性粒细胞绝对值、淋巴细胞数、单核细胞数、血小板数及网织红细胞、血红蛋白等进行比较。结果EPO治疗前治疗组与对照组的红系集落形成单位、红系爆式集落形成单位、粒-巨噬细胞集落形成单位、混合集落形成单位和巨核细胞集落形成单位的集落数差异无统计学意义（P〉0．05）。而治疗2周时，治疗组红系集落形成单位为（57±20）个，明显高于对照组[（34±13）个]（P〈0．05）；治疗组与对照组相比较，治疗期间白细胞总数、中性粒细胞绝对值、淋巴细胞数、单核细胞数及血小板数均无明显的变化（P〉0．05），而治疗组治疗1、2、3、4周后，网织红细胞数及血红蛋白均有显著提高（P〈0．05）；治疗第4周时，治疗组的血红蛋白高于对照组[（152±14）g／L，（128±11）g／L，P〈0．05]。结论从祖细胞水平及临床水平均证明了EPO治疗早产儿贫血的安全性及有效性。EPO可能作用于早产儿的红系晚期造血祖细胞及其以后阶段，进而使血红蛋白升高。

Objective To study the efficacy and safety of erythropoietin （EPO） in anemic premature infants, and explore the possible mechanism of erythropoietin on premature infants. Methods A randomized controlled study was prospectively conducted. Twenty-four premature infants were divided into treatment and control group with 12 in each. The treatment group received the same treatment as the control group besides receiving EPO 250 U/kg per time, 3 times weekly and 4 weeks totally. The number of circulating hematopoietic progenitor cells from 24 premature infants before and two weeks after treatment were determined by semisolid culture technique, and the counts of total white blood cell, neutrophil, lymphocyte, monocyte, platelet and reticulocyte, hemoglobin were compared between the two groups. Results Compared with the control group, EPO treatment for two weeks did not affect the number of burst forming unit-erythroid, colony forming unit-granulocyte/macrophage, colony forming unit-Mix and colony forming unit-megakaryocyte（P〉0. 05）, but there was a significant elevation in the number of colony forming unit-erythroid in the treatment group than in the control group （57±20 vs 34±13, P〈0.05）. The counts of total white cell, absolute neutrophil, lymphocyte, monocyte and platelet were not significantly decreased between the treatment and control group during the study of 4 weeks （P〉0. 05）. While all the infants received EPO had higher hemoglobine level and reticulocyte counts after one to four weeks of treatment （P〈0. 05）. In the fourth week, hemoglobin level of the treatment group was higher than controls （152±14） g/L vs （128±11） g/L, P〈0.05]. Conclusions EPO is effective and safe for anemic premature infants both on clinic and hematopoietic progenitor cell level. EPO could improve hemoglobin probably by taking effect on late erythroid progenitor cells and their later stage cells.