星形胶质细胞谷氨酸转运体表达下调是蛛网膜下腔出血（SAH）后神经损伤和认知障碍发生的重要机制。前期我们在大鼠SAH模型上发现海马区星形胶质细胞中组蛋白去乙酰化酶（HDACs）表达增高、组蛋白乙酰化水平降低、谷氨酸转运体表达下调，三者呈密切时程相关性，并且上调谷氨酸转运体表达可以显著改善SAH后动物认知障碍。结合他人研究，我们推测SAH后星形胶质细胞通过组蛋白乙酰化调节谷氨酸转运体的表达，进而参与神经认知障碍的发生。本课题拟在前期工作基础上，利用神经形态学和染色质免疫共沉淀技术观察SAH后谷氨酸转运体启动子区组蛋白乙酰化水平，进而运用动物行为学和神经电生理技术探讨HDACs抑制剂对神经认知功能和突触可塑性的影响，最后结合离体和在体实验探索组蛋白乙酰化调节谷氨酸转运体表达的分子机制。本研究希望能够从表观遗传学角度阐明SAH后神经认知障碍发生的机制，并为临床早期干预提供新策略。

Astrocytic glutamate transporter downregulation is an important mechanism of nerve injury and cognitive impairment after SAH. We found that the expression of histone deacetylase (HDACs) increased, the level of histone acetylation reduced, and the expression of glutamate transporters decreased in hippocampal astrocytes in rats after SAH, which are demonstrated closely-term relevance. And upregulating the expression of glutamate transporters can significantly improve cognitive dysfunction after SAH. In combination with other studies, we hypothesize that astrocytes regulate the expression of glutamate transporters after SAH through histone acetylation modulation, and which is involved in neurocognitive dysfunction. Based on previous work, this project intends to detect the histone acetylation level in the glutamate transporter promoter region with neural morphology and chromatin immunoprecipitation technique, then explore the effects of HDACs inhibitors on the cognitive function and synapse plasticity using the animal behavior tests and nerve electrophysiological experiments. Finally in vitro and in vivo experiments we explore the mechanisms of histone acetylation regulating the expression of glutamate transporters. This study hopes to elucidate the mechanism of cognitive impairment happening after SAH in the perspective of epigenetics, and provide new strategies for clinical intervention.