肢体缺血后处理通过激活MAPK途径保护大鼠海马区缺血性神经元  

The protective effect of limb ischemia postconditioning on ischemic neurons of rat hippocampus by activating MAPK pathway

作　　者：姜红升[1,2] 涂悦[2] 程世翔[2] 王毅[2] 令狐海瑞[1] 张赛[2] 

机构地区：[1]天津医科大学研究生院,天津300070 [2]武警医学院附属医院脑创伤与神经疾病研究所,天津300162

出　　处：《解剖科学进展》2011年第1期4-7,共4页Progress of Anatomical Sciences

基　　金：武警医学院院部重点项目(No.WYZ201002)

摘　　要：目的探讨肢体缺血后处理对缺血性神经元损伤的作用,观察大鼠海马CA1区ERK1/2的磷酸化及其蛋白表达的变化情况。方法健康成年雄性SD大鼠,随机分为假手术组(sham)、全脑缺血再灌组(四动脉闭塞全脑缺血模型ischemia/reperfusion,I/R)、肢体缺血后处理组(limb ischemia postconditioning,Lpost)、肢体缺血后处理+ERK1/2抑制剂组(Lpost+PD98059)。光镜下焦油紫染色法观察各组大鼠海马CA1区神经元存活情况;Western blot法检测海马CA1区ERK1、2磷酸化及蛋白表达情况。结果 Western blot结果显示脑缺血再灌注各时间点Lpost组p-ERK1/2水平均较I/R组高,且于再灌注后10min、1d出现两个高峰,给予ERK1/2上游激酶抑制剂PD98059后能够抑制再灌注后1dp-ERK1/2水平的升高;而各时间点各组ERK1/2水平之间无明显差异。焦油紫染色结果显示再灌注1d后,I/R组与sham组相比,海马CA1区存活神经元数量明显减少;Lpost组较I/R组海马CA1区存活神经元数量明显增加;而给予ERK1/2上游激酶抑制剂PD98059后(Lpost+PD98059)神经元生存数量较Lpost组大幅下降。结论肢体缺血后处理具有抗大鼠海马CA1区缺血性神经元损伤的作用,激活ERK1/2通路可能是其发挥保护作用机制之一。Objective To elucidate the protective effect of limb ischemia postconditioning on ischemic neurons of rat hippocampus and the possible mechanism related to ERK1/2 phosphorylation and protein expression in hippocampal CA1 region of the rats. Methods Adult male SpragueDawley rats were randomly divided into four groups：sham, ischemia/reperfusion（global cerebral ischemia by four-vessels occlusion,I/R）, limb ischaemia postconditioning（Lpost）, and Lpost＋PD98059 groups. Cresyl violet staining was used to observe survival neurons in hippocampal CA1 region of the rats by light microscope. ERK1/2 phosphorylation and its protein expression were detected by Western blot. Results Western blot analysis showed that the levels of p-ERK1/2 markedly increased after Lpost compared with I/R at the same time point, and the two peaks occurred at 10 min and 1d following reperfusion respectively, but the increase could be suppressed by PD98059. However, there is no significant change for levels of ERK1/2 between I/R and Lpost. Cresyl violet staining showed that I/R clearly reduced the number of survival neurons compared with sham at 1d of reperfusion in the hippocampal CA1 region, the number of survival neurons significantly increased in Lpost group compared with I/R, but decreased in Lpost＋PD98059 groups than in Lpost group. Conclusion Limb ischemia postconditioning could protect the cerebral ischemic neurons in hippocampal CA1 of rats, ERK1/2 is activated in this process.

关 键 词：缺血再灌注损伤 肢体缺血后处理 ERK1/2 SD大鼠 

分 类 号：R651.12[医药卫生—外科学]