ERK通路在脑缺血及缺血预处理沙土鼠海马神经元中的作用  

ROLE OF EXTRACELLULAR-SIGNAL REGULATED KINASE CASCADE ON CEREBRAL ISCHEMIA AND ISCHEMIC PRECONDITIONING IN HIPPOCAMPAL NEURON IN GERBILS

作　　者：李军[1] 曹红[1] 连庆泉[1] 王耀岐[2] 曾因明[2] 姚尚龙[3] 曾邦雄[3] 

机构地区：[1]温州医学院附属第二医院麻醉科,浙江温州325027 [2]徐州医学院江苏省麻醉学重点实验室,江苏徐州221002 [3]华中科技大学同济医学院协和医院麻醉科,湖北武汉430022

出　　处：《中国应用生理学杂志》2008年第2期237-242,共6页Chinese Journal of Applied Physiology

基　　金：浙江省自然科学基金资助项目(Y205200);江苏省教育厅科研基金资助项目(04KJB3200144)

摘　　要：目的:探讨细胞外信号调节激酶(ERK)通路在脑缺血及缺血预处理海马神经元中的作用。方法:雄性蒙古沙土鼠,随机分为假手术组(SH)、缺血/再灌注组(I/R)、缺血预处理组(IP)、PD98059组(PD)、溶剂对照组(VE组)、PD98059复合IP组(PIP),每组按再灌注15 min、2 h、4 h、6 h、1 d、3 d、5 d及7 d又分8个亚组。建立前脑缺血再灌注损伤模型,观察对行为学、组织学、p-ERK、HSP70、Fos及NF-κB表达的影响。结果:IP组鼠探索活动、CA1区凋亡神经元数及NF-κB阳性神经元数较I/R组明显减少(P<0.05),CA1区Fos阳性神经元数、HSP70及CA3/DG区p-ERK表达水平较I/R组明显增加(P<0.05)。PD组再灌注各点Fos阳性神经元数较I/R组明显减少(P<0.05)。再灌注1 d、3 d凋亡神经元数较I/R组明显增多(P<0.05)。PIP组各观察指标介于IP组及IR组间。结论:ERK通路在缺血后海马CA3/DG区的激活可能与该区的缺血耐受有关;诱导CA1区神经元Fos、HSP70表达,减少NF-κB生成是缺血预处理神经元保护作用的分子机制之一。Aim： To investigate the role of extracellular-signal regulated kinase（ERK） cascade on cerebral ischerna and ischemic preconditioning in hippocampal neuron. Methods： Male gerbils were randomly divided into sham group（SH）, ischemia/reperfusion group（ I/ R）, ischemia preconditioning group（IP）, specific antagonist of ERK-PD98059 （PD）, solvent control groups（VE group）, PD98059 combined with IP group（PIP）. Forebrain ischemia was induced by occlusion of bilateral common carotid arteries and confirmed by isoelectricity of EEG. Observations were carried out in each group 15min, 2 h, 4 h, 6 h, 1 d, 3 d, 5 d and 7 d after ischemia. Open field test was used to examine the spontaneous motor activity, the survival and apoptotic neurons, Fos and NF-kB masculine neurons in hippocampal CA1 region were counted, the expression of HSP70 in hippocampal CA1 region and p-ERK in hippocampal CA3/DG regions were detected by SABC immunocytochemical technique. Results： The spontaneous motor activity, the number of apoptotic neurons and NF-kB masculine neurons at 1 d, 3 d, 5 d, 7 d in CA1 region were much less in IP group than in I/R group（P〈 0.01）. The number of Fos masculine neurons at 15 min, 2 h, 4 h, 6 h, 1 d in CA1 region were significant more in IP group than in I/R group（P〈0.01）. The expressions of p-ERK and HSP70 were significantly higher in IP group than in I/R group. The number of Fos masculine neurons at each point were more and apoptotic neurons at 1 d, 3 d were less in PD group than in I/R group.Results of observation in PIP group were within IP group and I/R group. Conclusion： Activation of ERK in CA3/DG regions were related to ischemic tolerance. Induction of the expression of Fos and HSP70, decreasion of the product of NF-kB which might be one of the molecule mechanisms playing an important role in neural protection of ischemic preconditioning.

关 键 词：脑缺血/再灌注损伤 缺血预处理 ERK HSP70 FOS NF-κB 沙土鼠 

分 类 号：R973.2[医药卫生—药品] R963[医药卫生—药学]