摘要
目的 :由细胞周期调控入手探讨视黄醇类化合物诱导骨髓干 /祖细胞分化的分子机制。方法 :选择幼年小鼠骨髓细胞为研究对象 ,采用免疫组化、western blot等实验方法 ,观察 RA或 retinol灌胃给药后对骨髓细胞分化成熟的影响以及周期调控蛋白 cyclin D1及相应基因表达变化情况。结果 :ATRA和 retinol均可刺激骨髓有核细胞增殖活性 ,并诱导干 /祖细胞向粒系分化及粒系的终末分化 ;骨髓细胞 cyclin D1、CDK4和 RB基因表达呈时间剂量依赖性下调 ,而 p16、p2 1蛋白表达上调 ,且 ATRA作用优于 retinol。结论 :RA可能经 p Rb、p16等多因素反馈调节 cyclin D1和 CDK4表达 ,抑或直接同其发生作用 ,进而影响骨髓细胞增殖分化的进程。
Objective:In this report,the roles of cyclinD1 on the differentiation of bone marrow cells induced by all trans retinoic acid (ATRA) and retinol were studied to explore the molecular mechanism. Methods:CyclinD1、CDK4、CKIs and pRb protein expression were determined with immunocytochemistry or immunoblotting and the granulocyte macrophage colony forming unit(CFU GM) ability was examined in bone marrow cells treated 1~4 weeks by ATRA or retinol. Results:With the increasing of ATRA content in vivo,the formation of CFU GM was increased.Both ATRA and retinol decreased the expressions of cyclinD1、CDK4 and RB genes,increased the expressions of p16 and p21.The effects of ATRA in bone marrow cells were stronger than of retinol.Conclusions:ATRA and retinol could stimulate the proliferation and differentiation of murine bone marrow cells.The changes of expressions of cyclinD1、CDK4 and relative genes might be one of the molecular mechanisms of RA induced differentiation of bone marrow cells.
出处
《白血病》
2000年第2期79-82,共4页