HIF-1信号通路在介导DMOG动员MSCs中的作用机理-中国实验动物学报.docVIP

HIF-1信号通路在介导DMOG动员MSCs中的作用机理( 胡韶君1，余勤1，刘丽珍2，葛婷婷1 （1．浙江中医药大学学院杭州 3100532．浙江大学医学院附属第一医院骨髓移植中心杭州 310003摘要α/CXCR4和VEGF/VEGFR 通路在介导DMOG动员MSCs中的作用机理。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（P0.05）；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（P0.05）；同DMOG组比较，YC-1组HIF-1α浓度及蛋白表达显著降低（P0.05），AMD3100组SDF-1α浓度及蛋白表达显著降低（P0.05），SU5416组VEGF浓度及蛋白表达显著降低（P0.05）。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。 [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-lα； Mechanism of HIF-1 signaling pathway in mediating MSCs mobilization with DMOG HU Shao-jun1, YU Qin1, LIU Li-zhen2, GE Ting-ting1 （1 College of Life Science, Zhejiang Chinese Medical University, Zhejiang, Hangzhou, 310053, China; 2. Bone Marrow Transplantation Center, The First Affiliate Hospital, Medical School of Zhejiang University, Zhejiang, Hangzhou, 310003, China）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 (P0.05); 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 (P0.05). Compared with DMOG group, the concentration and protein expression of HIF-1α decreased significantly in YC-1 group (P0.05