三氧化二砷对小鼠骨髓造血微环境的影响

Effect of As_2O_3 on mouse bone marrow hemopoietic microenvironment

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:7μmol.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)。3μmol.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As2O3浓度是3μmol.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。

Objeotive To investigate the effect of As203 on normal mouse bone marrow stromal cells （BMSCs）. Methods BMSCs and colony-forming unit-granuloeyte 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 As203 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 As203 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 7μmol· L^1- As2O3, also the levels of G-CSF and IL-11 secreted by BMSC （P〈0.05）. The levels of G-CSF and IL-11 secreted by BMSCs were increased obviously if treated with 3μmol·L^-1 As2O3 continuously for 3 or 5 d, whereas without inereasing obviously when treated with 3μmol·L^-1 As2O3 continuously for 7 d and later （P〈0.05）. Oonolusion Lower concentration of As2O3 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 As203 eausing the max level of G-CSF and IL-11 is 3μmol·L^-1, The administration time when achieved the max levels of G-CSF and IL-11 is 5 d. The higher eoneentration of As2O3 and the elongation of the administration time can decrease the secretion of G -CSF and IL-11.