摘要
目的探讨低剂量羟基脲和丁酸钠联合应用对人红系细胞7种珠蛋白基因(ζ,α,ε,Gγ,Aγ,δ,β)mRNA表达的影响。方法以二步液体培养法培养的人红系祖细胞为体外模型,用台盼蓝拒染活细胞计数观察HU、丁酸钠单独或联合用药后对细胞生长的抑制作用;用RT-PCR比较用药前后7种珠蛋白基因mRNA的变化。结果低剂量联药组的细胞生长抑制率(26.44%)小于羟基脲和丁酸钠常规剂量单药组的抑制率(28.56%和38.80%)(P<0.05)。与未用药组(0.653±0.092和0.515±0.048)相比,联药组Gγ-和Aγ-mRNA的表达分别上调为1.203±0.018和0.915±0.088,差异有显著性(P<0.05);与羟基脲(1.305±0.016和0.956±0.029)、丁酸钠(1.193±0.070和0.883±0.012)常规剂量单药组之间的差异无显著性(P>0.05)。不同浓度药物对ζ,α,ε,δ和β-mRNA的诱导作用与各自未用药组之间的差异无显著性(P>0.05)。结论羟基脲和丁酸钠低剂量联合用药可上调红系细胞γ-珠蛋白基因的表达,尤其增加Gγ-mRNA的转录,且减轻了对细胞生长的抑制,而对ζ,α,ε,δ和β-珠蛋白基因无明显诱导作用。
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,β 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,δand β） （P〉0.05）. Conclusion Low-dose HU combined with NaB can up-regulate γglobin 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.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2009年第10期2073-2076,2081,共5页
Journal of Southern Medical University
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
β-thalassemia
hydroxyurea
sodium butyrate
combined administration
erythroid progenitor cells
globin gene
