重组人Flt3配体对微血管内皮细胞的抗辐射作用研究  

The influence of Flt3 ligand on proliferation of irradiated microvascular endothelial cells

作　　者：许志祥[1] 张学光[1] 强亦忠[1] 徐颖[1] 施勤[1] 朱剑昆[1] 丁天[2] 

机构地区：[1]苏州大学核医学生物技术重点实验室,医学生物技术研究所,江苏215007 [2]上海复旦大学生化系

出　　处：《中华放射医学与防护杂志》2001年第4期286-289,共4页Chinese Journal of Radiological Medicine and Protection

基　　金：国防科工委国防预研基金资助项目 (Y5 5 73 162 ) ; 国际原子能机构 (IAEA)基金资助项目 (CRP 9 0 2 5 )

摘　　要：目的　研究Flt3配体 (FL)对人微血管内皮细胞系细胞 (ECV)的抗辐射作用及其可能的作用机理。方法　用流式细胞仪分析ECV表面Flt3受体的表达 ;用MTT法观察FL对受照射ECV增殖的影响 ;用AnnexinV PI方法测定细胞凋亡 ,用RT PCR方法分析细胞凋亡基因bax和Bcl 2的改变。结果　ECV表达Flt3受体 ,FL能激发ECV增殖 ,ECV经 15Gy的照射后 ,FL能有效地拮抗照射对ECV增殖的抑制作用 ;同时照射后ECV的bax基因表达增加 ,bcl 2基因表达轻度降低。FL通过抑制bax基因的表达 ,降低辐射引起的ECV细胞凋亡。结论　FL通过抑制细胞凋亡 ,减轻辐射引起的ECV的损伤 ,可能在辐射损伤患者造血微环境的保护中具有应用价值。Objective\ To investigate the influence of FL on proliferation of irradiated microvascular endothelial cells (ECVs),and possible mechanism of FL in radiation protection of ECVs. Methods\ The ECVs were screened for Flt3 receptor expression by flow cytometric analysis.The proliferation of ECVs stimulated by FL was measured by the microculture tetrazolium assay (MTT).The apoptosis of ECVs caused by irradiation was measured with Annexin V PI.Two apoptosis related genes,Bcl XL and Bax,were also analyzed by RT PCR. Results\ Flt3 receptors were expressed on the surface of ECVs.FL stimulated the proliferation of ECVs at very low concentrations (0.5 15 ng/ml) with the maximum stimulation at 15 ng/ml.A significant increase in Bax activity and a decrease in Bcl XL activity were seen at 24 h and 48 h post irradiation,respectivety. When the culture medium with FL was added 2 h before or immediately after irradiation,the expression of Bax fell sharply at 24 h and 48 h post irradiation.The change in Bcl XL activity was not so marked and a mild increase in Bcl XL expression was seen only at 48 h post irradiation.FL inhibited the apoptosis of ECVs caused by irradiation and stimulated the proliferation of irradiated ECVs. Conclusion\ FL down regulates the expression of Bax in irradiated ECVs,and inhibits the apoptosis of the ECVs.Thus,FL may find a use in radio protection of hematopoietic cells via protection of the microvascular endothelial cells in the bone marrow microenvironment.\;

关 键 词：FLT3配体 造血微环境 微血管内皮细胞 抗辐射作用 细胞凋亡 细胞增殖 

分 类 号：R818.74[医药卫生—放射医学]