HIF-1信号通路在介导DMOG动员MSCs中的作用  

Mechanism of HIF-1 signaling pathway in mediating MSCs mobilization with DMOG

作　　者：胡韶君[1] 余勤[1] 刘丽珍[2] 葛婷婷[1] 

机构地区：[1]浙江中医药大学生命科学学院 [2]浙江大学医学院附属第一医院骨髓移植中心

出　　处：《中国比较医学杂志》2015年第1期9-14,I0002,I0003,共8页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金(81270566);教育部高校博士点专项科研基金(20130101120022)

摘　　要：目的探讨HIF-1及下游SDF-1α/CXCR4和VEGF/VEGFR通路在介导DMOG动员MSCs中的作用机制。方法将雄性SD大鼠,随机分为五组:生理盐水对照组、DMOG组、YC-1组、AMD3100组、SU5416组。分别采用CFU-F法与流式细胞术检测大鼠骨髓和外周血中MSCs的数量;ELISA法检测骨髓上清及外周血清中SDF-1α及VEGF蛋白浓度;Western blotting法检测骨髓细胞中HIF-1α、SDF-1α及VEGF蛋白表达水平。结果同NS组比较,DMOG组CFU-Fs数量显著增加,且CD45-CD90+细胞群比例增加(P<0.05);同DMOG组比较,YC-1组、AMD3100组、SU5416组CFU-Fs数量均显著减少,且CD45-CD90+细胞群比例降低(P<0.05);同DMOG组比较,YC-1组HIF-1α浓度及蛋白表达显著降低(P<0.05),AMD3100组SDF-1α浓度及蛋白表达显著降低(P<0.05),SU5416组VEGF浓度及蛋白表达显著降低(P<0.05)。结论 DMOG可能通过上调HIF-1α,从而调控其下游SDF-1α/CXCR4通路与VEGF/VEGFR通路诱导MSCs的动员。Objective To explore the role of HIF-1 and its downstream SDF-1α/CXCR4 and VEGF/VEGFR pathway in mediating MSC mobilization with DMOG. Methods Male SD rats were randomly divided into five groups：Normal saline control group,DMOG group,YC-1 group,AMD3100 group,SU5416 group. We used CFU-F assay and flow cytometry to determine the number of MSCs in rat bone marrow（ BM） and peripheral blood（ PB） in each group,respectively. The concentrations of SDF-1α and VEGF both in BM and PB serum in each group were detected by ELISA.Western blotting was used to test protein levels of HIF-1α,SDF-1α and VEGF in BM. Results Compared with NS group,the number of CFU-Fs as well as the percentage of CD45-CD90＋cells increased in DMOG group（ P〈0. 05）; Compared with DMOG group,the number of CFU-Fs as well as the percentage of CD45^-CD90^＋cells decreased in YC-1 group,AMD3100 group and SU5416 group（ P〈0. 05）. Compared with DMOG group,the concentration and protein expressionof HIF-1α decreased significantly in YC-1 group（ P〈0. 05）,the concentration and protein expression of SDF-1αdecreased significantly in AMD3100 group（ P〈0. 05）,the concentration and protein expression of VEGF decreased significantly in SU5416 group（ P〈0. 05）. Conclusion DMOG can induce MSCs mobilization possibly via upregulating the expression of HIF-1α and activating its downstream SDF-1α / CXCR4 and VEGF / VEGFR pathway.

关 键 词：间充质干细胞动员 DMOG 缺氧诱导因子-1Α 基质细胞衍生因子-1Α 血管内皮生长因子 

分 类 号：R332[医药卫生—人体生理学]