脑缺血后的神经元损伤中nNOS至关重要，但作用机制尚不清楚。课题组前期研究发现脑缺血后损伤的海马神经元中nNOS出现核转位，且nNOS可与Sox2结合，故提出nNOS入核后与核转录因子Sox2相互作用，通过调节Shh的转录，保护脑缺血后神经元免受凋亡。本课题拟首先在海马神经元损伤模型中分析nNOS与Sox2的表达及相互作用改变；接着分析nNOS与Sox2结合对Sox2介导的Shh转录及神经元凋亡的影响；最后在大鼠脑缺血模型中分析nNOS-Sox2复合物形成与脑缺血的关系。课题研究可为探求脑缺血神经元损伤的保护机制及防治的靶点提供理论依据和实验基础。

During the cerebral ischemia,nNOS plays an important role in the neuron apoptosis, but its regulatory mechanism remains unknown. Based on the finding of the nuclear translocation of nNOS in the neurons suffered from cerebral ischemic injury, and the nNOS may bind with Sox2, our group hypothesize that nNOS may enter the nucleus to interact with the transcription factor Sox2, regulate the transcription of Shh and thus play a neuroprotective role in the ischemia. In this subject, we will firstly investigate the interaction between nNOS and Sox2 in damaged hippocampal neurons model, and then analyses the effect on Sox2 acetylation. Based upon this,we may investigated the regulation of Shh transcription by interrupting the formation of the complex and analyse the biological significance of this event in neuron apoptosis. Finally, we shall intervene the formation of nNOS-Sox2 complex in the rat cerebral ischemic model to elucidate the neuroprotective role of the complex in brain ischemia. This research will provide both the theoretical and experimental bases to explore the protective mechanisms of neuronal injury after cerebral ischemia and the targets for treatment.

脑缺血后的神经元损伤中nNOS至关重要，但作用机制尚不清楚。课题组前期研究发现脑缺血后损伤的海马神经元中nNOS出现核转位，且nNOS可与Sox2结合，故提出nNOS入核后与核转录因子Sox2相互作用，通过调节Shh的转录，保护脑缺血后神经元免受凋亡。项目研究首先在海马神经元损伤模型中分析nNOS与Sox2的表达及相互作用改变；接着分析nNOS与Sox2结合对Sox2介导的Shh转录及神经元凋亡的影响；最后在大鼠脑缺血模型中分析nNOS-Sox2复合物形成与脑缺血的关系。研究结果表明在脑缺血所致的神经元损伤早期，nNOS进入细胞核，其可以与Sox2的相结合，增强了其转录活性，促进Shh的表达及其下游的保护基因的信号转导，保护脑缺血后海马神经元免受凋亡。课题研究可为探求脑缺血神经元损伤的保护机制及防治的靶点提供理论依据和实验基础。