短暂前脑缺血再灌注对大鼠海马脑区脑源性神经营养因子蛋白及mRNA表达的影响  

Effect of transient forebrain ischemia-reperfusion on expressions of brain-derived neurotrophic factor protein and mRNA in rat hippocampus

作　　者：严德萍 陈静[1] 马娜 高丽娟 李建国[1] YAN De-ping;CHEN Jing;MA Na;GAO Li-juan;LI Jian-guo(Key Laboratory of Cellular Physiology,Ministry of Education,Department of Physiology,Shanxi Medical University,Taiyuan 030001,Shanxi Province,China)

机构地区：[1]山西医科大学生理学系细胞生理学教育部重点实验室

出　　处：《中国生物制品学杂志》2020年第1期13-18,共6页Chinese Journal of Biologicals

基　　金：国家自然科学基金项目（81671231）;山西省‘1331工程’重点学科建设计划经费资助（XK201708）

摘　　要：目的探讨短暂前脑缺血再灌注(transient forebrain ischemia-reperfusion,I/R)对脑源性神经营养因子(brainderived neurotrophic factor,BDNF)蛋白及mRNA表达的影响,为进一步探索大鼠海马CA1区神经元损伤机制提供新的思路。方法将雄性SD大鼠随机分为control组、sham组和I/R组,利用Western blot和荧光定量PCR分析I/R后大鼠BDNF蛋白及mRNA表达的变化;染色质免疫共沉淀(chromatin immunoprecipitation,ChIP)试验检测I/R后大鼠BDNF基因启动子上H3K27的乙酰化水平。结果与control组相比,sham组大鼠CA1和CA3区BDNF蛋白和mRNA表达差异无统计学意义(P>0.05)。与sham组相比,I/R组大鼠CA1区BDNF蛋白表达显著下降(P<0.001),而CA3区BDNF蛋白表达增高(P<0.05);I/R组大鼠CA1区BDNF mRNAⅠ、Ⅱ和Ⅵ的表达均显著增高(P<0.01),而mRNAⅣ的表达显著下降(P<0.01),在CA3区4种mRNA均显著增高(P<0.01)。与sham组相比,I/R组大鼠CA1区BDNF启动子4的H3K27乙酰化水平显著下降(P<0.001),而CA3区BDNF启动子区域H3K27乙酰化水平增高(P<0.01)。结论I/R诱导大鼠海马CA1区BDNF蛋白及mRNA表达降低,并改变了BDNF基因启动子区乙酰化水平,为进一步研究BDNF表达降低引起神经元死亡的机制提供了新的方向。Objective To investigate the effect of transient forebrain ischemia-reperfusion(I/R)on expressions of brain-derived neurotrophic factor(BDNF)protein and mRNA in rat hippocampus,and provide a new ideal for the further study on the mechanism of neuronal lesion in rat CA1 region.Methods Male SD rats were randomly divided into control,sham and I/R groups.The expressions of BDNF protein and mRNA of rats after I/R were determined by Western blot and fluorescent quantitative PCR,while the acetylation level of H3K27 in BDNF promoter by chromatin immunoprecipitation(ChIP)assay.Results The expression levels of BDNF protein and mRNA in CA1 and CA3 regions of rats in sham group showed no significant difference with those in control group(P>0.05).Compared with that in sham group,the expression of BDNF protein in CA1 region of rats in I/R group decreased significantly(P<0.001),while that in CA3 region increased significantly(P<0.05).The expressions of BDNF mRNAsⅠ,ⅡandⅥin CA3 region of rats in I/R group increased significantly(P<0.01),while that of mRNAⅣdecreased significantly(P<0.01).However,in CA3 region,all the expressions of the four kinds of mRNAs increased significantly(P<0.01).As compared with tho se in sham group,the acetylation level of H3K27 in BDNF promoter 4 of CA1 region of rats in I/R group decreased significantly(P<0.001),while that in BDNF promoter of CA3 region increased significantly(P<0.01).Conclusion The I/R induces a decreased expression of BDNF protein and mRNA in the hippocampal CA1 region,and changes the acetylation level of BDNF promoter,which will provide new insight for further study on the mechanism of decreased BDNF expression inducing neuronal death.

关 键 词：脑源性神经营养因子蛋白 短暂前脑缺血再灌注 组蛋白乙酰化 海马 

分 类 号：R338[医药卫生—人体生理学]