临床神经外科杂志2019，Vol.16Issue(5)：410-414,419,6.DOI:10.3969／j.issn.1672-7770.2019.05.009
组蛋白去乙酰化酶2抑制剂在蛛网膜下腔出血模型动物认知障碍调节中的作用
Role of HDAC2i in regulation of cognitive impairment in animal models of subarachnoid hemorrhage
摘要
Abstract
Objective To investigate the effect of histone deacetylase HDAC 2 on the regulation of glutamate transporters in subarachnoid hemorrhage ( SAH) mice, and the potential protective effect of selective HDAC2i on the cognitive impairment post-SAH.Methods The SAH mouse model was established by internal carotid artery puncture.Western Blot and immunofluorescence staining were used to detect the expression of HDAC subtypes and GLT 1 in the hippocampal area of SAH mice, as well as their co-localization in astrocytes.Morris water maze( MWM) and open field test(OPT) were performed to examine the improvement of learning memory and depression in mice after intraperitoneally injection of a specific HDAC 2i for 10 days after SAH.Results Compared with Sham group, GLT1 in astrocytes in hippocampus was decreased following SAH ( P ＜0.05 -0.01), and HDAC subtypes were increased , with the most significant change in HDAC 2 (P＜0.05-0.01).Selective HDAC2 inhibitor treatment significantly reduced the escape latency in the training test( P＜0.05) and increased the traveling time in the target quadrant ( P＜0.05) in MWM, and increased the traveling distance (P＜0.05) and time( P＜0.05) in the central area in OPT of SAH mice.Meanwhile, the effect of HDAC2i in improving behavioral deficits in SAH mice can be blocked by GLT1 antagonist.Conclusion HDAC2 may participate in the regulation of animal cognitive impairment after SAH by mediating the expression of GLT 1 in astrocytes.Specific HDAC2i may exert the therapeutic effect of improving animal cognitive impairment after SAH.关键词
蛛网膜下腔出血/认知障碍/星形胶质细胞/组蛋白去乙酰化酶/谷氨酸转运体1Key words
subarachnoid hemorrhage / cognitive impairment/ astrocyte/ HDAC/ GLT1分类
医药卫生引用本文复制引用
赵学渊,蔡青,冯达云,吴勋,罗嘉宁..组蛋白去乙酰化酶2抑制剂在蛛网膜下腔出血模型动物认知障碍调节中的作用[J].临床神经外科杂志,2019,16(5):410-414,419,6.基金项目
国家自然科学基金青年项目(81500909) （81500909）
