AMPA受体介导的兴奋性毒性作用是缺氧缺血性脑损伤的重要机制。AMPA受体亚单位组成和/或数量的改变与突触重塑及神经元死亡密切相关，目前对AMPA受体运输的机制尚不清楚。我们的前期研究发现OGD后海马神经元AP4M1 mRNA和蛋白表达明显下调，且出现AP4M1的分布异常。有研究已证实，AP4可选择性的介导AMPA受体的运输，AP4的亚基缺失可引起神经发育缺陷或损伤。本课题旨在阐明缺氧缺血后AP4介导的AMPA运输异常在神经损伤中的分子机制。通过检测缺氧缺血后海马神经元AP4M1的表达变化及其与AMPA受体分布及其结构组成改变的关系，明确AP4M1通过AP4-TARP途径介导了AMPA受体的运输异常；并利用RNA干扰技术下调AP4M1表达,在细胞和在体不同层面进行验证。通过本研究阐明缺氧缺血后AP4介导AMPA受体运输的分子机制，为缺氧缺血性脑病的防治提供新途径。

AMPAR-mediated excitotoxicity is a mechanism critical to hypoxic_ischemic brain damage .Trafficking-mediated alterations in synaptic AMPAR subunit composition and/or number may represent a broad mechanism relevant to synaptic remodeling and neuronal death associated with a number of neurological disorders and diseases.However, the molecular mechanisms underlying receptors trafficking between intracellular compartments are still poorly defined.Our previous studys have found that the OGD induced AP4M1 down-regulation on hippcampal neuron. And other studies show that AMPA receptors are selectively transported to the synaptic membrane by AP4.Disruption of AP-4 complex integrity in nockout mice lacking the AP-4 beta subunit leads to mislocalization of AMPA glutamate receptors on neuron.The subject aims to illustrate the molecular mechanism of hypoxic_ischemic brain damage in AP4 mediated AMPA trafficking abnormality.Through the detection of AP4 expression and changes of AMPAR subunit composition and distribution on hippcampal neuron after OGD, clear that AMPA receptor trafficking abnormality is mediated by AP4M1 through AP4-TARP pathway. Using RNA interference to down-regulate AP4M1 expression and then in the cells and in vivo verification. Through this study to elucidate the molecular mechanism of AP4M1 mediated the AMPA receptor trafficking after hypoxia-ischemia and provide new ways for prevention and treatment of hypoxic-ischemic encephalopathy.