sB7-H3加速颅脑损伤后肢体骨折愈合的分子机制研究

项目名称： sB7-H3加速颅脑损伤后肢体骨折愈合的分子机制研究

项目编号： No.81471862

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郭国宁

作者单位： 中国人民解放军第三军医大学

项目金额： 69万元

中文摘要： 颅脑损伤后可加速骨折愈合，但其机制尚未清楚。骨免疫学是近来提出的概念，B7-H3是新近鉴定的具有免疫抑制的膜分子，我们前期研究发现，B7-H3既可抑制T细胞活化，同时也促进骨髓干细胞分化为成骨细胞；此外，在颅脑损伤合并股骨骨折患者血浆中，也发现高水平的可溶性B7-H3（sB7-H3）。我们推测颅脑损伤后分泌sB7-H3，通过破坏的血脑屏障，促进骨折部位成骨。本研究拟收集颅脑损伤合并骨折及单独骨折患者的血清，分析sB7-H3水平与骨折愈合的关系；采用sB7-H3体外刺激骨髓干细胞或T细胞，分析其促成骨细胞分化的分子机理；建立开放骨折并落体撞击脑损伤的B7-H3基因敲除小鼠模型，探讨缺乏B7-H3作用后对骨折愈合的影响；并使用B7-H3Ig融合蛋白免疫WT模型小鼠，分析其对骨折愈合的促进作用。本研究将阐明sB7-H3促颅脑损伤后加速骨折愈合的分子机理，为临颅脑损伤合并肢体骨折的治疗提供新策略。

中文关键词： 颅脑创伤；创伤修复；骨折愈合

英文摘要： Accelerated fracture healing after traumatic brain injury is confirmed clinical phenomenon. But the mechanism is not yet clear. Bone immunology is proposed recently.B7-H3 is a newly identified immune molecules. Our previous study found that, B7-H3 not only can inhibit T cell activation, but also can promote bone marrow stem cells differentiate into bone cells; In addition, high levels of soluble B7-H3 (sB7 -H3) was found in the plasma of head injury combined with femur fracture. We speculate that sB7-H3 is secreted by injuried brain will promote osteogenesis through destroying the blood-brain barrier. This study intends to collect the patient's serum alone fractures and traumatic brain injury and fracture, then to analysis the relationship of sB7-H3 levels and fracture healing; Using sB7-H3 in vitro to stimulate bone marrow stem cells or T-cells, which contributed to the analysis of the molecular mechanism of bone cell differentiation; Establish B7H3 knockout mouse model of open fractures and brain injuries to investigate the effect of the lack of B7-H3 on fracture healing; Using the fusion protein B7-H3Ig WT mouse model to analyze the fracture healing facilitating role. This study will elucidate the molecular mechanism of sB7-H3 accelerated fracture healing with brain injury, provide new strategies for the clinical head injury with limb fractures.

英文关键词： brain injury;trauma repair;bone healing