HIF-1α/SDF-1/CXCR4信号轴在颅脑损伤时骨折加速愈合中的作用及实验研究

项目名称： HIF-1α/SDF-1/CXCR4信号轴在颅脑损伤时骨折加速愈合中的作用及实验研究

项目编号： No.81501897

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 徐炜

作者单位： 上海交通大学

项目金额： 18万元

中文摘要： 临床发现颅脑损伤后骨折愈合速度较单纯骨折明显增快，机制可能与颅脑损伤后机体处于低氧环境有关。HIF-1α（缺氧诱导因子-1α）及其下游基因SDF-1（基质细胞衍生因子-1）在低氧环境下参与组织修复，两者与CXC趋化因子受体4（CXCR4,SDF-1的特异受体）形成HIF-1α/SDF-1/CXCR4信号轴。前期研究证实在颅脑损伤合并股骨骨折模型中，骨折周围组织中HIF-1α，SDF-1的表达均明显高于单纯骨折模型，且与骨痂形成情况存在正相关，假如能明确此信号轴在骨折愈合中的作用，将为骨折不愈合的治疗提供新的思路。本研究拟在前期基础上，建立颅脑损伤合并股骨骨折的小鼠模型，从分子、组织水平、体内试验等方面，对此信号轴介导骨髓间质干细胞向骨折断端趋化进行深层次的分析。旨在阐明HIF-1α/SDF-1/CXCR4信号轴是颅脑外伤时骨折加速愈合的一种新机制，为骨折延迟愈合或者不愈合提供新的治疗靶点。

中文关键词： 低氧诱导因子-1α；基质细胞衍生因子-1；信号通路；创伤性脑损伤；骨折愈合

英文摘要： In clinical observation,patients with fracture after traumatic brain injury were found to show accelerated fracture recovery than simplex fracture.The potential mechanisms probably related to the hypoxia environment after the traumatic brain injury.Hypoxia inducible factor-1α(HIF-1α), and its downstream gene Stromal cell-derived factor-1(SDF-1) can promote tissue repairing in the hypoxia environment，by interacting with CXCR4(the recepter of SDF-1),they compse the signal pathway of HIF-1α/SDF-1/CXCR4.Our former research has confirmed that the express of HIF-1α and SDF-1 in tissues around fracture in TBI/fracture model is significantly higher than in fracture only model,and this promoted callus formation in a dose-dependent manner.Based on the previous research,a mice model of femoral fractures combined with traumatic brain injury and a model of femoral fractures only will be established in this study,and the role and mechanism of HIF-1α/SDF-1/CXCR4 pathway in driving bone marrow mesenchymal stem cells(MSC) to the callus will be investigated from molecule level,tissue level,and animal level.By understanding the mechanism of this pathway in accelerating the recovery of fracture, hopefully we could provide a potential strategy of treatment to delayed union of fractures.

英文关键词： hypoxia inducible factor-1α;Stromal cell-derived factor 1;Signal pathway ;Traumatic Brain Injury ; Fracture Healing