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陈乐文,杨敏光,戴雅玲,何肖君,贾微微,林华伟,柳维林.电针调控前额叶组蛋白乙酰化修饰改善血管性痴呆大鼠认知功能的实验研究[J].中国康复医学杂志,2021,(8):923~930
电针调控前额叶组蛋白乙酰化修饰改善血管性痴呆大鼠认知功能的实验研究    点此下载全文
陈乐文  杨敏光  戴雅玲  何肖君  贾微微  林华伟  柳维林
福建中医药大学康复医学院,福州市,350122
基金项目:国家自然科学基金项目(81873355);中央本级重大增减支项目(2060302)
DOI:10.3969/j.issn.1001-1242.2021.08.004
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摘要:
      摘要 目的:探讨电针百会、神庭穴干预对血管性痴呆(vascular dementia,VD)大鼠认知行为学、前额叶组蛋白H3K9乙酰化修饰,以及突触可塑性相关蛋白表达的影响。 方法:健康雄性Sprague-Dawley大鼠24只,随机分为假手术组、模型组、电针组,每组各8只。模型组和电针组采用2-VO(结扎双侧颈总动脉)方法制备血管性痴呆模型,假手术组仅分离颈总动脉但不结扎。电针组采用电针百会、神庭穴干预4周。采用Morris水迷宫测试工作记忆能力,新物体识别测试干预后物体识别记忆能力;免疫印迹法检测前额叶突触可塑性相关蛋白α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体1(α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid receptor 1,AMPAR1)、N-甲基-D-天冬氨酸受体1(N-methyl-D-aspartic acid receptor 1,NMDAR1)、N-甲基-D-天冬氨酸受体2B (N-methyl-D-aspartic acid receptor 2B,NMDAR2B),以及组蛋白H3K9乙酰化修饰相关蛋白CBP(CREB-binding protein,CREB结合蛋白)、E1A结合蛋白P300(E1A binding protein P300,P300)、组蛋白去乙酰基转移酶1(histone deacetylase 1,HDAC1)的表达水平。 结果:干预前,与假手术组相比,模型组、电针组Morris水迷宫工作记忆测试逃避潜伏期延长(P<0.05),后两组间逃避潜伏期无显著性差异(P>0.05)。干预后,与模型组相比,电针组Morris水迷宫工作记忆测试逃避潜伏期缩短(P<0.05),电针组新物体识别指数升高(P<0.05)。干预后,与模型组相比,电针组前额叶突触可塑性相关蛋白NMDAR1和NMDAR2B表达上升(P<0.05),AMPAR1表达无显著性差异(P>0.05);组蛋白H3K9乙酰化修饰水平升高(P<0.05),组蛋白乙酰基转移酶CBP(P<0.05)和P300(P<0.05)表达上升,而组蛋白去乙酰基转移酶HDAC1表达无显著性差异(P>0.05)。 结论:电针百会、神庭穴干预可以改善血管性痴呆大鼠认知功能,可能与调控前额叶组蛋白H3K9乙酰化修饰,提高突触可塑性有关。
关键词:电针  突触可塑性  血管性痴呆  组蛋白乙酰化
Effects of electroacupuncture on histone acetylation modification in prefrontal lobe to improve cognitive function after vascular dementia in rats:An experimental study    Download Fulltext
College of Rehabilitation Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou,Fujian,350122
Fund Project:
Abstract:
      Abstract Objective:To observe the effects of electroacupuncture (EA) at the Baihui and Shenting acupoints on cognitive function, acetylation modification of histone H3K9, and expression of synaptic plasticity related proteins in prefrontal cortex of rats with vascular dementia. Method:A total of 24 male Sprague-Dawley rats were randomly divided into the sham operation group, model group and EA group,8 rats in each group. 2-VO method was used to establish the vascular dementia model in the model group and the EA group. In the sham group, the common carotid artery was isolated but not ligated. In the EA group, Baihui and Shenting acupoints were carried out for 4 weeks. Morris water maze was used to test working memory before and after intervention, and new object recognition was used to test object recognition memory after intervention. After sampling, the expressions of prefrontal synaptic plasticity related proteins AMPAR1, NMDAR1, and NMDAR2B, and histone H3K9 acetylation-modified related proteins H3K9ac, HDAC1, CBP, and P300 were detected by Western Blot. Result:Before intervention, compared with the sham group, the escape latency in Morris water maze test was increased in the model group and the EA group (P<0.05), and there was no significant difference in the escape latency between the latter two groups (P>0.05). After intervention, compared with the model group, the escape latency in Morris water maze test was decreased in the EA group (P<0.05), and new object recognition index in the EA group was increased (P<0.05). After the intervention, compared with the model group, the expressions of prefrontal synaptic plasticity related protein NMDAR1 and NMDAR2B were increased in the EA group (P<0.05), but the expression of AMPAR1 was no significant difference (P>0.05). The expressions of histone H3K9 acetylation and histone acetyltransferases CBP (P<0.05) and P300 (P<0.05) were increased in the EA group compared to the model group after the intervention, but the expression of histone deacetylase HDAC1 was no significant difference (P>0.05). Conclusion:EA at the Baihui and Shenting acupoints can improve the cognitive function of rats with vascular dementia, which may be related to the regulation of prefrontal modification of histone H3K9 acetylation and synaptic plasticity.
Keywords:electroacupuncture  synaptic plasticity  vascular dementia  histone acetylation
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