线粒体铁蛋白对脑外伤后铁诱导氧化应激损伤的神经保护作用及机制研究

Traumatic brain injury (TBI) is one of the most serious diseases that pose a threat to the public health. In addition to the primary injury caused by damage to the brain tissue, there are a series of secondary injuries inducing disability or death. Oxidative stress in TBI plays a key role in such secondary injury pathogenesis. Previous studies have shown that highly reactive free radical reactions induced by excessive iron accumulation after TBI can cause neural damages via Fenton’s reaction. Current researches have focused on how to reduce the neural damages caused by such iron-induced pathogenesis. In previous studies, we found that the mitochondrial ferritin (FtMt) involved in sub-cellular iron regulatory pathway played an important role in both diagnosis and treatment of diseases caused by iron metabolism imbalance. In view of this, both in vitro and in vivo experiments will be adopted to study the effect of FtMt on ferrous oxidase activity, iron storage and mineralization as well as the relationship between FtMt expression and neuro-degeneration occuring after TBI. We aim to provide theoretical and practical evidences for clinical diagnosis and treatment through detecting the FtMt expression level in brain tissues after TBI, exploring its neuro-protective effect and detailed mechanisms on iron-induced oxidative stress as well as making up for defects of the brain iron regulatory pool.

创伤性颅脑损伤（TBI）是危害人民健康的重大难治性疾病。除原发伤外，尚有一系列致残、致死的继发性损伤相继发生。TBI后氧化应激是导致上述继发性损伤的重要发病机制之一。既往研究表明，创伤后脑铁过量累积可通过Fenton反应产生高活性自由基反应类型引起神经元损伤。如何减轻TBI后铁诱导的自由基产物所导致的神经损害已成为目前该领域的研究热点之一。申请者前期研究发现，线粒体铁蛋白（FtMt）在亚细胞水平上对铁代谢通路研究和铁平衡失调所引发的疾病在诊治方面具有重要作用。本研究拟采用体内、外试验研究TBI模型中FtMt表达改变与伤后皮层神经元神经退行性改变之间的关系，针对FtMt亚铁氧化酶活性及贮铁、铁矿化等功能展开研究，检测其在颅脑损伤脑组织中表达水平的改变，探讨其对TBI后铁诱导的氧化应激损伤的神经保护作用及其机制，分析其可否通过弥补脑组织铁离子库自身调控缺陷，为临床诊治提供重要的理论、实践依据。

创伤性颅脑损伤（TBI）是危害人民健康的重大难治性疾病。除原发伤外，尚有一系列致残、致死的继发性损伤相继发生。TBI后氧化应激是导致上述继发性损伤的重要发病机制之一。既往研究表明，创伤后脑铁过量累积可通过Fenton反应产生高活性自由基反应类型引起神经元损伤。如何减轻TBI后铁诱导的自由基产物所导致的神经损害已成为目前该领域的研究热点之一。线粒体铁蛋白（FtMt）在亚细胞水平上对铁代谢通路研究和铁平衡失调所引发的疾病在诊治方面具有重要作用。本研究采用体内、外试验研究TBI模型中FtMt表达改变与伤后皮层神经元神经退行性改变之间的关系，检测其在颅脑损伤脑组织中表达水平的改变，初步阐明其对TBI后铁诱导的氧化应激损伤的神经保护作用及机制，分析其通过弥补脑组织铁离子库自身调控缺陷，为临床诊治提供重要的理论、实践依据。