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锂对液体培养系统中小鼠造血作用的影响。

The effect of lithium on murine hematopoiesis in a liquid culture system.

作者信息

Levitt L J, Quesenberry P J

出版信息

N Engl J Med. 1980 Mar 27;302(13):713-9. doi: 10.1056/NEJM198003273021303.

DOI:10.1056/NEJM198003273021303
PMID:6965517
Abstract

Lithium carbonate has been shown to increase granulocyte production. We studied the effect of lithium on murine hematopoiesis in a liquid culture system providing for the prolonged growth of stem cells and their progeny. After one week of incubation, lithium, at a supernatant concentration of 1 mmol per liter, increased murine pluripotent stem cells (CFU-S, or colony-forming units in spleen) to 232 per cent of control values (P less than 0.001), granulocyte-monocyte progenitor cells (CFU-C, or colony-forming units in culture) to 218 per cent of control values (P less than 0.0001), granulocytes to 125 per cent of control values (P less than 0.01), and megakaryocytes to 246 per cent of control values (P less than 0.001). These increases were associated with transient elevations in colony-stimulatory activity. Prolonged exposure to lithium (three to 12 weeks) was associated with a dose-dependent progressive depletion of stem cells and their progeny. Lithium enhancement of granulopoiesis may be explained by primary stimulation of the pluripotent stem cell. Prolonged proliferative stress induced by lithium when the stem-cell reserve is limited may be associated with diminished replicative potential of the stem cells and rapid depletion of cells.

摘要

碳酸锂已被证明可增加粒细胞生成。我们在一个能使干细胞及其后代长期生长的液体培养系统中研究了锂对小鼠造血作用的影响。孵育一周后,上清液中锂浓度为每升1毫摩尔时,小鼠多能干细胞(脾集落形成单位,即CFU-S)增加至对照值的232%(P小于0.001),粒细胞 - 单核细胞祖细胞(培养集落形成单位,即CFU-C)增加至对照值的218%(P小于0.0001),粒细胞增加至对照值的125%(P小于0.01),巨核细胞增加至对照值的246%(P小于0.001)。这些增加与集落刺激活性的短暂升高有关。长期暴露于锂(三至十二周)与干细胞及其后代的剂量依赖性渐进性耗竭有关。锂对粒细胞生成的增强作用可能是由对多能干细胞的直接刺激所解释。当干细胞储备有限时,锂诱导的长期增殖应激可能与干细胞复制潜力的降低和细胞的快速耗竭有关。

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