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