【摘要】 为了探讨川芎嗪对放射损伤小鼠骨髓基质细胞血管内皮细胞生长因子 (VEGF)表达的影响及其促进放射损伤小鼠骨髓微环境修复的机制和信号通路 ,采用Westernblot法和流式细胞术对放射损伤小鼠骨髓基质细胞中VEGF表达水平 ,粘着斑激酶 (FAK)和促分裂原活化蛋白激酶 (MAPK)活性变化及骨髓基质细胞凋亡率和细胞周期改变进行分析 ,同时观察川芎嗪对其影响。实验结果表明 ,放射损伤后小鼠骨髓基质细胞VEGF表达明显低于正常水平 ,随时间推移而逐渐升高 ,但照射后第 14天仍未恢复正常 ,而服川芎嗪组VEGF表达在第 14天时已接近正常水平 ;骨髓基质细胞中磷酸化FAK和磷酸化MAPK表达亦有相同变化趋势。放射损伤后 ,骨髓基质细胞停滞于G0 G1期 ,S期减少 ,凋亡率明显增加。随时间推移 ,G0 G1期细胞比例呈由高到低的变化 ,凋亡率也逐渐降低 ,至 14天仍未恢复正常。用川芎嗪治疗后 ,骨髓基质细胞S期合成活跃 ,凋亡率明显下降 ,第 14天时恢复更明显 ,接近正常水平。结论 :川芎嗪可通过促进骨髓基质细胞VEGF的表达加速照射后骨髓造血微环境恢复 ,其机制可能是通过VEGF诱导FAK和MAPK磷酸化途径实现的。更多还原

【Abstract】 To evaluate the effect of Ligustrazine on the expression of VEGF in bone marrow stromal cells (BMSCs) of radiation injured mice and to explore the effect of VEGF on the recovery of hematopoiesis and the mechanism of signal transduction, the protein expression of VEGF, focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK) in BMSCs were assayed by Western blot, the cell cycle and apoptosis rate of BMSCs were tested by flow cytometry. The effect of Ligustrazine on the hematopoiesis was evaluated at the same time. The results showed that the protein expression of VEGF in BMSCs was decreased significantly after irradiation and increased slowly with the time. The value in Ligustrazine-treated group almost reached normal level, but it remained lower than that in control group on day 14. The changes of phosphorylated FAK and MAPK protein expression had the same tendency. After 60 Co γ-irradiation, the BMSCs were arrested in G 0-G 1 phase and apoptosis rate increased; these values recovered slowly with the time and remained higher than that in normal control group on day 14. The recovery of these values in Ligustrazine-treated group was sooner than that in irradiated control group, and they almost reached to the normal levels on day 14. It is concluded that irradiation could inhibit the expression of VEGF in BMSCs and induce apoptosis. The Ligustrazine promotes the recovery of bone marrow microenvironment probably by increasing the expression of phosphorylated FAK and MAPK in BMSCs.更多还原