最近人类全基因组关联分析（GWAS）研究发现，组蛋白去乙酰化酶9（HDAC9）与大血管脑卒中密切相关。我们前期的预实验也发现，小鼠脑缺血后HDAC9的表达增加，而HDAC9基因敲除能保护缺血性脑损伤，但其具体机制还不清楚。我们根据已有的文献、预实验及对HDAC9分子结构研究，提出假设：在缺血性脑损伤中，CaMKⅡ的激活促使HDAC9丝氨酸位点的磷酸化，导致HDAC9与DNA结合位点分离，从而提高MEF2等下游基因的转录活性，进而发挥神经保护作用。我们拟利用HDAC9基因敲除小鼠、RNA干扰、基因过表达、蛋白质谱等技术从整体、细胞和分子水平上对以上假设进行验证。本课题的完成，将进一步深入认识HDAC9在中枢神经系统中的作用，并可从抑制HDAC9的活化出发，为治疗缺血性脑损伤等疾病提供新的方向。

In the recently human genome wide association (GWAS) study, it was found that histone deacetylase 9 (HDAC9) is closely associated with large vessel stroke. Our pilot study also found that, after focal cerebral ischemia, the expression of HDAC9 was increased, while HDAC9 gene knockout protected cerebral ischemic injury, but the mechanism is not clear at percent. Based on the other’s and our pilot works, and the molecular structure of HDAC9, we propose a hypothesis: CaMK II activation promotes HDAC9 serine phosphorylation, leading to HDAC9 separated from DNA binding sites, and then enhances the transcriptional activity of MEF2, which plays a neuroprotective effects in the cerebral ischemia injury. In this project, HDAC9 knockout mice, RNA interference gene over-expression and mass spectrometry technologies were used to approve the hypothesis. From this project, it will help to know the role of HDAC9 in central nervous system, and then provide a new treatment to cerebral ischemia injury by blocking HDAC9 activation.