MAPK家族在沙土鼠前脑缺血再灌注期间海马神经元表达的动态变化

目的:探讨MAPK家族三成员在脑缺血再灌注期间其于海马不同亚区神经元的表达及活性变化。方法:采用沙土鼠双侧颈总动脉阻断缺血再灌注损伤模型。随机分为假手术组(SH)、3min缺血组(IA)及5min缺血组(IS);各组根据再灌注15 min、2 h、4 h、6 h、1 d、3 d、5 d及7 d又分8个亚组(n=8)。在预定时间点行免疫组化法测定海马各亚区MAPK蛋白及其磷酸化水平。结果:三组海马三区ERK、JNK及p38三种蛋白的总体水平在缺血后再灌注期间未发生改变。IS组磷酸化ERK(p-ERK)在缺血后CA3/DG区颗粒细胞及神经元树突上表达,而在CA1区几无表达;磷酸化JNK(p-JNK)在缺血后再灌注7 d内CA3区神经元均有少量表达,在CA1区表达量多并有二次表达高峰(2 h和1 d);磷酸化p-38(p-p38)缺血后再灌注期间的表达区域与p-JNK相似,有一次表达高峰(2 h)。IA组三激酶磷酸化水平均较IS组明显减少(P<0.05),表达规律相同。结论:脑缺血再灌注可导致MAPK三成员在海马各亚区差异性表达,此特征可能与MAPK的作用相关。

Dynamiccbanges and expressions of mitogen-activated protein kinase superfamily during forebrain ischemia-reperfusion in gerbil''''s hippocampus

Objective:To explore the changes and expressions of mitogen-activated protein kinase(MAPK) superfamily during forebrain ischemia-reperfusion in gerbil's hippocampus.Methods:Forebrain ischemia was induced by occlusion of bilateral common carotid arteries.Gerbils were randomly divided into sham group(SH),3 minutes ischemia group(IA) and 5 minutes ischemia group(IS).The gerbils were reperfused in 15 min,2h,4h,6h,1d,3d,5d and 7d in each group following ischemia(n=8).The expression of MAPK in hippocampus was detected by SABC immunocytochemical technique.Results: The immunoreactivity of ERK,JNK and p38 in three regions of hippocampus had no changes whether with ischemia or not,but the levels of their phosphorylation and expression regions had obviously altered after ischemia between two ischemia groups.Phospho-ERK(p-ERK) was only expressed in neurofibrils and granules of CA3/DG regions,p-ERK wasn't expressed in CA1 region.The high levels of p-ERK and prolonged expressional time were observed in CA3/DG regions in IS group.Phospho-JNK(p-JNK) was appeared little in CA3 region and was not changed during 7 days after ischemia,but high levels of p-JNK and activation biphasely(2 h and 1d after reperfusion) in CA1 region were observed in group IS.The regions and intracellular distribution of phospho-p38(p-p38) were resemble with that of p-JNK,but it had only one phase increasing(2 h after reperfusion).The level of three kinases in group IA were less than that in group IS,but regularity of expression resemble with that in group IS.Conclusion: The characteristic of three MAPK kinases expression shows variability in different hippocampal regions which correlate with their effects during ischemia-reperfusion.