血小板生成素基因在体内的表达及对造血祖细胞增殖活性的影响  

Expression of Human Thrombopoietin cDNA in Mice and the Effects on Proliferation of Hematopoietic Progenitor Cells

作　　者：赵建增 刘丽[1] 陈惠仁[1] 梅英杰[1] 

机构地区：[1]空军总医院临床分子生物学研究中心

出　　处：《中国生物化学与分子生物学报》1998年第2期117-121,共5页Chinese Journal of Biochemistry and Molecular Biology

摘　　要：探讨了从肌肉组织植入的人血小板生成素（ＴＰＯ）基因在小鼠体内的表达规律，以及对造血祖细胞增殖活性的影响．基因在导入后的２４小时内就开始转录，先于血小板、血液ＴＰＯ浓度、及造血祖细胞的变化．所表达的ＴＰＯ在血液中的聚积可持续４周以上．巨核祖细胞，粒系祖细胞都出现２周左右的增殖增长，长于血小板计数的升高，但红系祖细胞的变化不明显．这些结果显示，基因治疗过程中血小板计数等变化源于ＴＰＯ的表达及刺激，而在此期间一些调控机制被激活，对血小板形成的平衡发挥作用．Thrombopoietin(TPO) has been considered as a specific growth factor for megakaryocyte lineage.Research by several groups suggested that gene delivery provided a new pathway for TPO infusion to animals and human body,however,overexpression of the gene would bring harmful results.The study is to clarify the in vivo expression course of the transferred hTPO gene and the possible effects on hematopoietic progenitor cells.The gene started to transcript early within 24 h after delivery,preceding to the changes of platelet count and colony forming units of megakaryocyte (CFU MK).Transcription in local muscle tissue and accumulation of circulating TPO could be detectable 4 weeks later.Colony forming units of granulocyte and macrophage (CFU GM) were also increased,however,there is no significant change in burst forming units of erythrocyte.Uprising of CFU MK and CFU GM lasted for 2 weeks which were longer than the augment of platelet count.These data implied that the promotion of platelet production resulted from the expression of transferred TPO gene and some regulatory mechanisms were activated to balance the abnormally high thrombopoiesis.

关 键 词：血小板生成素 基因治疗 造血祖细胞 细胞增殖 

分 类 号：Q592.1[生物学—生物化学] R456[医药卫生—治疗学]