以凋亡诱导因子为靶点防治新生儿脑损伤的研究

项目名称： 以凋亡诱导因子为靶点防治新生儿脑损伤的研究

项目编号： No.31271152

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 朱长连

作者单位： 郑州大学

项目金额： 95万元

中文摘要： 应用条件性基因敲除或者基因突变小鼠的缺氧缺血脑损伤模型，以凋亡诱导因子及辅因子为研究靶点，采用免疫组织化学、细胞生物学、生物物理学、分子生物学以及动物神经行为测定等方法，结合荧光标记、光共聚焦显微镜、无偏差体视显微镜及线粒体呼吸功能测定等技术，探讨凋亡诱导因子及辅因子尤其是脑特异性凋亡诱导因子的亚型、线粒体膜腔隙转运蛋白40与脑发育和脑损伤的关系，并根据凋亡诱导因子与辅因子亲环蛋白A的表面分子结构合成能与凋亡诱导因子或者亲环蛋白A竞争性结合的小分子肽，进行抑制神经细胞死亡的体内外实验，为新生儿脑损伤的防治提供理论基础和新的措施。

中文关键词： 新生儿；脑损伤；线粒体；凋亡诱导因子；凋亡

英文摘要： Despite major improvements in maternal care, obstetrics and neonatology, the number of newborn children suffering from brain injuries occurring around birth is increasing. One reason for this is that more children born much too early and survive. Neonatal brain injury is a frequent cause of cerebral palsy, which is the most common cause of severe disability in children. Considerable efforts have been focused on treatments for neonatal brain injury; however, to date, most have been unsuccessful. The current therapy for preterm brain injury is mainly supportive. There is an urgent need for developing neuroprotective approaches for this condition. Apoptosis plays a far greater role in the immature brain than in the adult brain. Apoptosis-Inducing Factor (AIF) is very important for neuronal cell death which could be a targeted protective strategy for limiting neonatal brain injury. We have identified a brain-specific form of this protein, AIF2. We have also identified a protein not previously studied in the brain, Mia40, which binds to AIF. In this proposal, we will use AIF conditional knock out mice as well as Mia40 heterozygous mice and their wild type controls to produce neonatal hypoxia ischemia brain injury model. The effect of AIF2 or Mia40 on mitochondrial respiration, neural stem / progenitor cells prolifera

英文关键词： Neonate；Brain injury；Mitochondria；Apoptosis inducing factor；Apoptosis