全脑缺血复灌不同时间对大鼠海马神经元损伤及JNK通路的影响

目的探讨大鼠全脑缺血和复灌不同时间对海马神经元损伤、C-Jun氨基末端激酶（JNK）表达以及JNK激活的影响。方法采用四血管法（4-vessel-occlusion，4-vo）法制作大鼠全脑缺血模型，随机将51只SD大鼠分成假手术组、缺血组和缺血再灌注组，用Western blot检测海马组织JNK的表达和P-JNK的含量。另取9只大鼠缺血10min或缺血20min后复灌7d，甲醛灌注固定后取海马组织用于组织学评价。结果JNK在全脑缺血10min表达明显增加，缺血20min时达到峰值；全脑缺血20min复灌阶段JNK在复灌6h表达明显增加并达到-高峰，复灌12h到达最高峰；P-JNK含量在全脑缺血20min后复灌1h达到高峰，复灌12h再次出现高峰。结论20min全脑缺血后JNK高表达持续时间延长，JNK激活时间更早，更为显著，表明长时间缺血时JNK通路介导的损害作用更大。

Effects of different duration of global cerebral ischemia and reperfusion on neuronal injury and JNK pathway in rat hippocarnpue

Objective TO investigate the expression of C-Jun N-terminal kinase （JNK） and p-JNK in hippocampus and hippocampal neuronal death after prolonged global cerebral ischemia/reperfusion in rats. Methods Transient global cerebral ischemia was induced by four-vessel occlusion method. Fifty four SD rats weighing 250-320g were randomly divided into 3 groups： sham operation group, ischemia group and the isohemia/reperfusion group. The expression of JNK and p-JNK was examined by Western blotting method. The surviving neurons in hippocampal CA1 area were counted by HE staining after 10min or 20min ischemia and 7d reperfusion. Results The expression of JNK increased after 10 min ischemia, and the peak appeared at 20min of ischemia; the expression of JNK in the Jschemia/reperfusion group presented two peaks, with an initial peak at 6 h, and the second, larger peak at 12 h of reperfusion. The peak for the expression of p-JNK in the ischemia/reperfusion group presented at 1h of reperfusion, then decreased a little, and peaked again at 12h of reperfusion. Conclusion The results suggested JNK pathway is associated with neuron death after long time ischemia.