【摘要】 目的 研究脑缺血及预缺血再灌注后大鼠海马脑区细胞外信号调节激酶5(ERK5)的磷酸化(激活)规律以及NMDA受体抑制剂盐酸氯胺酮(开他敏)对其激活的影响。方法 采用SD大鼠四动脉结扎缺血及预缺血模型,给药组大鼠在缺血前20 min腹腔给予盐酸氯胺酮30 mg/kg。用免疫印迹法分析不同条件下大鼠海马ERK5的蛋白表达量和激活情况;焦油紫染色观察缺血及预缺血对大鼠海马神经元的作用。结果 盐酸氯胺酮显著抑制了预缺血再灌注后ERK5的激活,而ERK5的蛋白表达量在以上相同处理条件下无明显变化;焦油紫染色观察示预缺血对大鼠海马神经元具有保护作用。结论 预缺血再灌注具有神经元保护作用,这种保护作用与NMDA受体有关,为临床治疗脑中风提供理论依据。更多还原

【Abstract】 Objective To investigate the law governing the phosphorylation(activation)of extracellular signalregulated protein kinase 5(ERK5)in rat hippocampus in response to ischemia preconditioning and ischemia/reperfusion(I/R)and the effect of NMDA receptor ketamine hydrochloride on ERK5 activation.Methods Animal model of ischemia and ischemia preconditioning was established by four-vessel occlusion(4-VO)in Sprague-Dawley rats.Western blot assay was used to examine the protein expression levels and activation of ERK5 in different conditions;cresyl violet staining was employed to demonstrate the effect of ischemia preconditioning and ischemia/reperfusion(I/R)on rat hippocampal neurons.The rats in the administration group were intraperitoneally injected with ketamine hydrochloride 20 min before ischemia.Results ERK5 activation in cytoplasm was significantly inhibited by NMDA receptor ketamine hydrochloride following ischemia preconditioning and I/R,while no marked change was observed in the protein expression of ERK5 under the same treatment conditions;cresyl violet staining showed that neurons in the hippocampus subjected to ischemia preconditioning were significantly protected compared with those without preconditioning.Conclusion Ischemia preconditioning has neuroprotective effect on ischemia-reperfusion induced neuronal death and this effect is correlated with NMDA receptors.These findings might provide theoretic basis for clinical therapies for stroke.更多还原