[1]赵学渊,蔡青,冯达云,等.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):410-419.[doi:10.3969/j.issn.1672-7770.2019.05.009]
 ZHAO Xue-yuan,CAI Qing,FENG Da-yun,et al.Role of HDAC2i in regulation of cognitive impairment in animal models of subarachnoid hemorrhage[J].Journal of Clinical Neurosurgery,2019,16(5):410-419.[doi:10.3969/j.issn.1672-7770.2019.05.009]
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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()
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《临床神经外科杂志》[ISSN:1672-7770/CN:32-1727/R]

卷:
16
期数:
2019年第5期
页码:
410-419
栏目:
脑血管病专题
出版日期:
2019-10-15

文章信息/Info

Title:
Role of HDAC2i in regulation of cognitive impairment in animal models of subarachnoid hemorrhage
作者:
赵学渊蔡青冯达云吴勋罗嘉宁
710032 西安,空军军医大学基础医学院五大队十九队(赵学渊);空军军医大学第二附属医院神经外科(蔡青,冯达云,吴勋,罗嘉宁)
Author(s):
ZHAO Xue-yuan CAI Qing FENG Da-yun et al.
Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xian 710032, China
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1
Keywords:
subarachnoid hemorrhage cognitive impairment astrocyte HDAC GLT1
分类号:
R743.34
DOI:
10.3969/j.issn.1672-7770.2019.05.009
文献标志码:
A
摘要:
【摘要】目的 探讨组蛋白去乙酰化酶(histone deacetylase,HDAC)2在蛛网膜下腔出血(subarachnoid hemorrhage,SAH)模型小鼠谷氨酸转运体(glutamate transporter,GLT)的调节中的作用,以及HDAC2抑制剂(HDAC2i)对SAH后认知障碍的保护作用。方法采用颈内动脉穿刺法建立小鼠SAH模型,Western Blot和免疫荧光染色检测SAH小鼠海马区各亚型HDAC、GLT1的表达水平及其在星形胶质细胞中的定位。用Morris水迷宫和旷场行为学试验检测新型特异性HDAC2i腹腔注射10 d对SAH小鼠学习记忆、抑郁情绪的改善作用。结果与假手术组(Sham)相比,SAH组小鼠各时间点海马组织星形胶质细胞的GLT1表达水平降低(P<0.05-0.01),各亚型HDAC表达水平增高(P<0.05-0.01),HDAC2变化最为显著;HDAC2i治疗后SAH小鼠水迷宫训练逃逸时间显著降低(P<0.05),目标象限活动时间增加(P<0.05)。同时HDAC2i改善SAH小鼠行为学异常的作用又可以被GLT1拮抗剂阻断。结论HDAC2可能通过调控星形胶质细胞的GLT1表达,参与SAH后小鼠认知障碍的调节。特异性HDAC2i可能具有改善SAH后认知障碍的作用。
Abstract:
Abstract: ObjectiveTo investigate the effect of histone deacetylase HDAC2 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. MethodsThe 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 GLT1 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 HDAC2i for 10 days after SAH. ResultsCompared 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 HDAC2(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. ConclusionHDAC2 may participate in the regulation of animal cognitive impairment after SAH by mediating the expression of GLT1 in astrocytes. Specific HDAC2i may exert the therapeutic effect of improving animal cognitive impairment after SAH.

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更新日期/Last Update: 2019-10-15