三氧化二砷对小鼠骨髓造血微环境的影响

目的：了解三氧化二砷（As₂O₃）对正常小鼠骨髓基质细胞的影响。方法：采用体外小鼠骨髓基质细胞贴壁培养法、粒-单系祖细胞集落培养法和ELISA方法，观察不同浓度As₂O₃作用不同时间后CFU-F、骨髓基质细胞支持的CFU-GM及其分泌G-CSF、IL-11的数量变化。 结果：7 μmol·L^-1的As₂O₃使CFU-F、骨髓基质细胞支持的CFU-GM产率及其 分泌的G-CSF、IL-11的水平较对照组显著下降 (P<005)。3 μmol·L^-1的As₂O₃用药3 d或5 d骨髓基质细胞分泌G-CSF、IL-11的水平较对照组显著增加(P<0.05)，持续用药7 d后，则无显著增加。结论：较低浓度As₂O₃对骨髓基质细胞集落形成及其支持CFU-GM生成无明显抑制作用，反而刺激骨髓基质细胞分泌G-CSF和IL-11，引起分泌高峰的As2O3浓度是3 μmol·L^-1，高峰时间为用药5 d，As₂O₃给药浓度过大、用药时间过长，均可使造血因子分泌量下降。 

Effect of As2O3 on mouse bone marrow hemopoietic microenvironment

Objective To investigate the effect of As_2O_3 on normal mouse bone marrow stromal cells(BMSCs).Methods BMSCs and colony-forming unit-granulocyte macrophage (CFU-GM) were cultured in vitro to observe the quantitative changes of colony-forming unit-fibroblast(CFU-F) and CFU-GM after BMSCs were treated with different concentrations of As_2O_3 respectively;the quantitative changes of CFU-GM supported by BMSCs and granulocyte colony stimulating factor(G-CSF) and IL-11 secreted by BMSCs were also observed after the progenitor cells supported by BMSCs were treated with As_2O_3 for 3,5 and 7 d,respectively.Results The productions of CFU-F and CFU-GM supported by BMSCs were decreased obviously when treated with 7 μmol·L~(-1) As_2O_3,also the levels of G-CSF and IL-11 secreted by BMSC(P<0.05).The levels of GCSF and IL-11 secreted by BMSCs were increased obviously if treated with 3 μmol·L~(-1) As_2O_3 continuously for 3 or 5 d,whereas without increasing obviously when treated with 3 μmol·L~(-1) As_2O_3 continuously for 7 d and later(P<0.05).(Conclusion Lower) concentration of As_2O_3 has not significant inhibitory effects on clone forming of BMSCs and the productions of CFU-GM supported by BMSCs,but stimulates BMSCs to secret G-CSF and IL-11.The concentration of As_2O_3 causing the max level of G-CSF and IL-11 is 3 μmol·L~(-1).The administration time when achieved the max levels of G-CSF and IL11 is 5 d.The higher concentration of As_2O_3 and the elongation of the administration time can decrease the secretion of G-CSF and IL-11.