DRα1-MOG-35-55治疗在外伤性脑损伤中对减小病灶大小及改善神经功能缺损的作用
发布时间：2018-07-24 12:48
【摘要】：背景和目的:外伤性脑损伤(TBI)能够导致严重的神经功能缺损而且并缺乏有效的治疗。炎症反应在TBI后的脑部二次损伤中的关键的病理事件中起到了重要作用,因此,抗炎治疗也是针对TBI的新型治疗方向。在近期的研究中,我们已经证明了人类白细胞抗原DRα1结构域连接MOG-35-55肽(DRα1-MOG-35-55)构建体在多发性硬化和缺血性卒中的动物模型中减少中枢神经系统炎症和减轻组织损伤的作用。这项研究的目的在于探究DRα1-MOG-35-55治疗对TBI模型小鼠预后的改善情况。方法:通过液压打击在C57BL/6小鼠上构建TBI模型。评估神经功能缺损,病灶体积和免疫反应来探究DRα1-MOG-35-55治疗的疗效和神经保护机制。结果:DRα1-MOG-35-55构建体能够显著改善TBI术后神经功能缺损并减小脑部病灶体积。在DRα1-MOG-35-55治疗的TBI术后小鼠体内,能看到巨噬细胞浸润减少,其表达的CD74和CD86也减少。相反,接受DRα1-MOG-35-55治疗后TBI模型小鼠中CD206的表达增多。DRα1-MOG-35-55治疗能够减少TBI术后脑组织内巨噬细胞的浸润。值得注意的是,DRα1-MOG-35-55能够减少循环中的CD11b+细胞的数量及其表达CD74的水平。结论:我们实验结果显示DRα1-MOG-35-55在TBI小鼠模型中的治疗可能是有效的。仍然需要进一步的研究来证明DRα1-MOG-35-55对TBI的治疗效果。
[Abstract]:Background and objective: traumatic brain injury (TBI) can lead to severe neurological impairment and lack of effective treatment. Inflammation plays an important role in the key pathological events of brain secondary injury after TBI. Therefore, anti-inflammatory therapy is also a new treatment direction for TBI. In recent studies, we have demonstrated the role of human leukocyte antigen Dr 伪 1 domain coupled MOG-35-55 伪 1-MOG-35-55 (Dr 伪 1-MOG-35-55) construction in reducing inflammation and tissue damage in multiple sclerosis and ischemic stroke in animal models. The aim of this study was to explore the improvement of prognosis in TBI model mice treated with Dr 伪 1-MOG-35-55. Methods: TBI model was established on C57BL/6 mice by hydraulic attack. To investigate the therapeutic effect and neuroprotective mechanism of Dr 伪 1-MOG-35-55 by evaluating nerve function defect, focus volume and immune response. Results the ratio Dr 伪 1-MOG-35-55 construction could significantly improve the neurological deficit and reduce the volume of brain focus after TBI. The macrophage infiltration and the expression of CD74 and CD86 in Dr 伪 1-MOG-35-55 treated mice after TBI were decreased. On the contrary, the increase of CD206 expression in TBI model mice after treatment with Dr 伪 1-MOG-35-55. Dr 伪 1-MOG-35-55 treatment could reduce the infiltration of macrophages in brain tissue after TBI. It is worth noting that Dr 伪 1-MOG-35-55 can reduce the number of circulating CD11b cells and the level of CD74 expression. Conclusion: our results suggest that Dr 伪 1-MOG-35-55 may be effective in the treatment of TBI mice. Further research is still needed to demonstrate the efficacy of Dr 伪 1-MOG-35-55 in the treatment of TBI.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R651.15
[Abstract]:Background and objective: traumatic brain injury (TBI) can lead to severe neurological impairment and lack of effective treatment. Inflammation plays an important role in the key pathological events of brain secondary injury after TBI. Therefore, anti-inflammatory therapy is also a new treatment direction for TBI. In recent studies, we have demonstrated the role of human leukocyte antigen Dr 伪 1 domain coupled MOG-35-55 伪 1-MOG-35-55 (Dr 伪 1-MOG-35-55) construction in reducing inflammation and tissue damage in multiple sclerosis and ischemic stroke in animal models. The aim of this study was to explore the improvement of prognosis in TBI model mice treated with Dr 伪 1-MOG-35-55. Methods: TBI model was established on C57BL/6 mice by hydraulic attack. To investigate the therapeutic effect and neuroprotective mechanism of Dr 伪 1-MOG-35-55 by evaluating nerve function defect, focus volume and immune response. Results the ratio Dr 伪 1-MOG-35-55 construction could significantly improve the neurological deficit and reduce the volume of brain focus after TBI. The macrophage infiltration and the expression of CD74 and CD86 in Dr 伪 1-MOG-35-55 treated mice after TBI were decreased. On the contrary, the increase of CD206 expression in TBI model mice after treatment with Dr 伪 1-MOG-35-55. Dr 伪 1-MOG-35-55 treatment could reduce the infiltration of macrophages in brain tissue after TBI. It is worth noting that Dr 伪 1-MOG-35-55 can reduce the number of circulating CD11b cells and the level of CD74 expression. Conclusion: our results suggest that Dr 伪 1-MOG-35-55 may be effective in the treatment of TBI mice. Further research is still needed to demonstrate the efficacy of Dr 伪 1-MOG-35-55 in the treatment of TBI.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R651.15
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