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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: To investigate the molecular mechanism of retinoid-induced differentiation of bone marrow stem / progenitor cells by cell cycle regulation. Methods: Bone marrow cells from juvenile mice were selected as experimental subjects. The effects of RA or retinol on the differentiation and maturation of bone marrow cells and the expression of cyclin D1 and its related genes were observed by immunohistochemistry and western blot. Happening. RESULTS: Both ATRA and retinol stimulated the proliferation of bone marrow nucleated cells, and induced the differentiation of stem / progenitor cells into granulocytic and telophase. The expression of cyclin D1, CDK4 and RB genes in bone marrow cells were down-regulated in a dose- The p16, p21 protein expression is up-regulated, and ATRA is better than retinol. Conclusion: RA may regulate the expression of cyclin D1 and CDK4 through multiple factors such as p Rb and p16, or directly affect the process of proliferation and differentiation of bone marrow cells.