缺血再灌注对大鼠海马组蛋白脱乙酰酶磷酸化水平的影响  

Effects of ischemia-reperfusion on the phosphorylation level of histone deacetylase in the hippocampus of rats

作　　者：李建国[1,2] 陈静 孟金凤[1,2] 张倩倩 燕子 赵欣[1,2] 张宇[1,2] Li Jianguo;Chen Jing;Meng Jinfeng;Zhang Qianqian;Yan Zi;Zhao Xin;Zhang Yu(Department of Physiology,Shanxi Medical University,Taiyuan 030001,China;Key Laboratory of Cellular Physiology Ministry of Education,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学生理学系,太原030001 [2]山西医科大学细胞生理学教育部重点实验室,太原030001

出　　处：《神经解剖学杂志》2022年第2期135-141,共7页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81671231);山西省应用基础研究计划项目(201901D211320);山西省回国留学人员科研资助项目(2020-081,2021-080)。

摘　　要：目的:研究缺血再灌注(I/R)后海马不同区域I类和II类组蛋白脱乙酰酶(HDAC)的表达和功能,以阐明HDAC在I/R性神经元损伤中的作用机制。方法:制备脑I/R模型,采用Western Blot分析HDAC和磷酸化HDAC(p-HDAC)在海马CA1、CA3和DG区的表达,在体分别给予HDAC(1、2、3、4、7)特异性抑制剂(Parthenolide、CAY10683、RGFP966、Tasquinimod、MS-275)后,采用尼氏染色检测其对海马神经元存活的影响。结果:在CA1区和CA3区,I/R组p-HDAC1、p-HDAC2、p-HDAC3、HDAC4、p-HDAC4和p-HDAC7的表达比假手术(sham)组显著增高(P<0.01)。在DG区,sham组HDAC1、p-HDAC1、p-HDAC2、p-HDAC3、HDAC4、p-HDAC4、HDAC7和p-HDAC7的表达显著高于sham组CA1区和CA3区的表达(P<0.05)。I/R组CA1区存活神经元数目比sham组低(P<0.01),HDAC抑制剂可显著减弱CA1区神经元死亡(P<0.01),而对CA3和DG区存活神经元数目无显著影响(P>0.05)。结论:I/R可通过p-HDAC(1、2、3、4、7)影响大鼠海马CA1区神经元存活,抑制其功能能够减弱神经元死亡。Objective:To study the expression and function of class I and II histone deacetylase(HDAC)in different regions of the hippocampus after ischemia-reperfusion(I/R)to clarify the mechanism of HDAC in I/R injury.Methods:A cerebral I/R model was prepared.Western Blot was used to analyze the expression of HDAC and phospho-HDAC(p-HDAC)in hippocampal CA1,CA3 and DG regions.After treatment with specific inhibitors of HDAC(1,2,3,4,7)(Parthenolide,CAY10683,RGFP966,Tasquinimod,and MS-275)in vivo,Nissl staining was used to detect its effects on the survival of neurons in the hippocampus.Results:In the CA1 and CA3 regions,the expression of p-HDAC1,p-HDAC2,p-HDAC3,HDAC4,p-HDAC4,and p-HDAC7 in the I/R group was significantly higher than that in the sham group(P<0.01).In the DG region,the expressions of HDAC1,p-HDAC1,p-HDAC2,p-HDAC3,HDAC4,p-HDAC4,HDAC7,and p-HDAC7 in the sham group were significantly higher than those in the CA1 and CA3 regions of the sham group(P<0.05).The number of surviving neurons in the CA1 region of the I/R group was lower than that of the sham group(P<0.01).HDAC inhibitors significantly reduce the number of neuronal cell death in the CA1 region(P<0.01),but had no significant effects on the number of surviving neurons in the CA3 and DG regions(P>0.05).Conclusion:I/R affects the survival of neurons in the hippocampal CA1 region of rats through p-HDAC(1,2,3,4,7),and inhibiting its function can reduce neuronal cell death.

关 键 词：缺血再灌注 海马 组蛋白脱乙酰酶 组蛋白脱乙酰酶抑制剂 神经元死亡 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]