脯氨酸羟化酶抑制剂对小鼠间充质干细胞的动员作用  

Effect of Prolylhydroxylase Inhibitor on Mobilization of Mesenchymal Stem Cells in Mice

作　　者：刘伟[1] 余勤[1] 刘丽珍[2] 周丽萍[1] 胡韶君[1] 

机构地区：[1]浙江中医药大学生物工程学院,杭州310053 [2]浙江大学医学院附属第一医院

出　　处：《浙江中医药大学学报》2013年第12期1371-1376,共6页Journal of Zhejiang Chinese Medical University

基　　金：国家自然科学基金(81270566);浙江省自然科学基金(LQ13H080001)~~

摘　　要：[目的]探讨脯氨酸羟化酶抑制剂——二甲基乙二酰基甘氨酸(dimethyloxaloylglycine,DMOG)对小鼠间充质干细胞(mouse mesenchymal stem cells,mMSCs)的动员作用。[方法]ICR小鼠随机分为对照组及3个DMOG动员剂量组(20、40、80mg·kg-1)。不同剂量的DMOG每天一次在固定的时间段腹腔内注射入ICR小鼠,对照组给予相同体积的生理盐水。采用流式细胞术与成纤维细胞集落形成单位法检测不同浓度DMOG处理后小鼠外周血与骨髓中MSCs数量,Western blotting法检测骨髓细胞中HIF-1α、SDF-1α及VEGF蛋白的表达,ELISA法检测骨髓上清及外周血清中SDF-1α及VEGF蛋白的浓度。[结果]流式细胞术与成纤维细胞集落形成单位法检测发现不同剂量的DMOG处理7d后小鼠外周血与骨髓中MSCs数量较对照组显著增加(P<0.05),且CD45-CD90+细胞群比例升高(P<0.05)。同时Western blotting法及ELISA法检测发现小鼠骨髓HIF-1α、SDF-1α表达上调,VEGF浓度升高(P<0.05)。[结论]DMOG对小鼠间充质干细胞具有动员作用,可能与通过上调HIF-1α,从而调控其下游相关通路有关。[Objective]To explore the effect of prolylhydroxylase inhibitor-dimethyloxal ylglycine（DMOG） on mesenchymal stem cells mobilization in mice. [Methods]ICR mice were randomly assigned into 3 mobilization groups（20, 40, 80mg＆#183;kg-1 DMOG） and a control group. ICR mice were treated with differ-ent doses of DMOG daily in a fixed time interval by intraperitoneal injection, while the control group was given the same volume of physiological saline in-stead. We used flow cytometry and CFU-F assay to determine the number of MSCs in peripheral blood and bone marrow in each group. We also detected the expression of HIF-1α, SDF-1αand VEGF both in peripheral blood and bone marrow in each group by Western blotting and ELISA.[Results]The de-tection of flow cytometry and CFU-F assay showed that the number of MSCs in peripheral blood and bone marrow increased significantly in mice treated with different doses of DMOG for 7 days, with higher percentages of CD45-CD90＋cells. In addition, Western blotting and ELISA analysis identified that the protein level of HIF-1αand SDF-1αand the concentrations of VEGF were increased in bone marrow. [Conclusion] DMOG can induce MSC mobilization, possibly via up-regulating the expression of HIF-1αand activating its downstream pathways.

关 键 词：间充质干细胞 动员 缺氧诱导因子-1Α 成纤维细胞集落生成单位 HYPOXIA INDUCIBLE factor-1α 

分 类 号：R331[医药卫生—人体生理学]