摘要
Abstract
Objective To investigate the effects of combined use of low-dose hydroxyurea (HU) and sodium butyrate (NaB) on the expression of 7 globin genes (ζ,α,ε,~Gγ,~Aγ,δ, and β) in human erythroid progenitor cells. Methods Human erythroid progenitor cells were cultured using a two-step liquid culture system and treated with HU and NaB either alone or in combination. The inhibitory effects of the agents on the cell growth were monitored with trypan blue exclusion assay, and the changes in the mRNA of the 7 globin genes were detected using RT-PCR. Results Low-dose HU combined with NaB resulted in significantly lower inhibition rate of the erythroid progenitor cells than routine dose HU and NaB used alone (28.56% and 38.80%, respectively, P<0.05). Compared with untreated cells (0.653±0.092 and 0.515±0.048), HU combined with NaB significantly increased the expression of ~Gγ-and ~Aγ-mRNA (1.203±0.018 and 0.915±0.088, respectively, P<0.05), and HU and NaB used alone produced similar effects (1.305±0.016 and 0.956±0.029 for HU, and 1.193±0.070 and 0.883± 0.012 for NaB, P>0.05). HU and NaB, either used alone or in combination or at different doses, caused no significant changes in the other globin genes (ζ,α,ε,δ and β) (P>0.05). Conclusion Low-dose HU combined with NaB can up-regulate γ globin gene expression, especially ~Gγ-mRNA expression, to decrease the growth inhibition on human erythroid progenitor cells in vitro, but produces no significant effect on the expressions of ζ,α,ε,δ and β genes.关键词
β-地中海贫血/羟基脲/丁酸钠/联合用药/红系祖细胞/珠蛋白基因Key words
β-thalassemia/ hydroxyurea/ sodium butyrate/ combined administration/ erythroid progenitor cells/ globin gene分类
医药卫生
