外源性VEGF促小鼠造血干细胞动员  

Exogenous VEGF Promotes Hematopoietic Stem Cell Mobilization

作　　者：朱晓健[1] 李翊[1] 游泳[1] 李青[1] 曾辰[1] 仲照东[1] 邹萍[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院血液病学研究所,湖北武汉430022

出　　处：《中国实验血液学杂志》2014年第1期154-159,共6页Journal of Experimental Hematology

基　　金：湖北省卫生厅项目资助(JX5B07)

摘　　要：本研究旨在探讨外源性注射血管内皮生长因子(VEGF)对正常小鼠造血干细胞的动员作用及其对免疫功能的影响。将正常C57BL/6J小鼠随机分为正常对照组、VEGF短期组(5 d)和VEGF长期组(27 d);实验组腹腔注射VEGF 100 ng/d,正常对照组腹腔注射PBS;应用全自动血细胞分析仪检测不同时间小鼠外周血白细胞数量和淋巴细胞的比例,流式细胞术检测各组外周血和脾脏的造血干细胞、淋巴细胞亚群、调节T细胞(Treg)和髓源抑制性细胞(MDSC)的数量,显微镜观察对照组和长期组脾脏形态学改变,测定脾指数。结果表明:注射VEGF后,小鼠外周血WBC数明显升高,第3天达峰值;短期组外周血和脾脏中干细胞比例显著高于正常对照组(P<0.05);长期组脾脏增大,脾指数升高(P<0.05),可见明显髓外造血;给药后,小鼠外周血淋巴细胞总数没有明显改变,但长期组CD3+细胞比例和CD3+/B220+细胞比值下降;实验组外周血和脾脏CD4+CD25+Treg和Gr-1+CD11b+MDSC水平均增高(P<0.05),在长期组升高更明显(P<0.05)。结论:外源性VEGF可提高造血干细胞的动员,同时上调多种抑制性免疫细胞,导致机体免疫功能发生改变。This study was aimed to investigate the effect of exogenous VEGF on hematopoietic stem cell mobilization and immune system.The C57BL/6J mice were randomly divided into the normal control group,VEGF short-term group （5 d） and VEGF long-term group （27 d）.Mice in the experimental group were injected ip with VEGF （100 ng/d） ;mice in control group were injected ip with PBS.The white blood cell （WBC） count and the ratio of lymphocyte in the peripheral blood at different time point were assayed by hemacytometer.The percentage of hematopoietic stem cell （HSC）,lymphocyte subgroup,regulatory T cell （Treg）,myeloid-derived suppressor cells （MDSC） in the peripheral blood and spleen of different groups were detected by flow cytomertry.The morphological changes of spleen and spleen index of mice in the control and long-term group were observed by microscopy.The results showed that the absolute number of WBC in the peripheral blood of mice significantly increased after injection of VEGF,and the peak value was at day 3.The percentage of Lin-Sca-1 ＋ CD117 ＋ cells in the peripheral blood and spleen of the long-term group were significantly higher than that in the normal control group （P ＜ 0.05）.The spleen of the mice in VEGF long-term group was larger than that of the control group,the spleen index also increased （P ＜ 0.05）,and remarkable extramedullary hematopoietic signs were found in the HE stained sections.There was no significant change in the total ratio of lymphocytes in the peripheral blood after injection,but the percentage of CD3 ＋ cells and the CD3 ＋/B220 ＋ ratio in the longterm group deceased; the percentages of Treg and Gr-1 ＋ CD11b＋ MDSC in the experimental groups increased （P ＜0.05）,which more significantly increased in the long-term group than that in the short-term group （P ＜ 0.05）.It is concluded that the exogenous VEGF promotes hematopoietic stem cell mobilization,and at same time up-regulates the many kinds of suppressive immune cell levels which

关 键 词：血管内皮生长因子 造血干细胞动员 免疫调节 髓源抑制性细胞 

分 类 号：R331.2[医药卫生—人体生理学]