氯胺酮的神经保护作用及其对p38蛋白磷酸化激活的影响  

Effects of ketamine on neuroprotection and phospho-p38 protein activation induced by oxygen-glucose deprivation in rat hippocampal slices

作　　者：吴兴军[1] 陈红专[1] 陆阳[1] 

机构地区：[1]上海第二医科大学药物研究所,上海200025

出　　处：《中国临床药理学与治疗学》2005年第1期15-19,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金项目 (№ 3 0 3 7173 1) ;上海第二医科大学 -上海交通大学联合科研基金项目 (№ 2 0 0 3HZJJ0 0 2 ) ;上海市教委学科建设专项基金项目 (№JY2 0 0 1)

摘　　要：目的 :研究NMDA受体拮抗剂氯胺酮对大鼠海马脑片缺糖缺氧 (OGD)损伤的神经保护作用及其对p38蛋白磷酸化激活的影响。方法 :采用大鼠海马脑片体外OGD损伤模型 ,TTC染色抽提法观察氯胺酮对海马脑片OGD损伤时的神经保护作用 ,免疫印迹法研究“缺血再灌注”不同时间大鼠海马脑片中p38磷酸化激活变化情况 ,以及氯胺酮对p38磷酸化激活的影响。结果 :氯胺酮显著抑制海马脑片OGD损伤所致的A值降低 ,p38蛋白在缺血再灌注后磷酸化激活增加 ,再灌注 15min后开始上升 ,2h仍可见持续表达。氯胺酮剂量为 5、10 μmol·L-1时 ,能显著抑制p38蛋白磷酸化激活 (P <0 .0 5 )。结论 :氯胺酮具有一定的神经保护作用 ,其保护作用可能与抑制海马神经元p38蛋白的磷酸化激活有关。AIM : To investigate the effects of NMDA receptor antagonist ketamine on neuroprotection and the activation of phospho p38 protein induced by oxygen glucose deprivation(OGD) in the rat hippocampal slices. METHODS : The OGD model of rat hippocampal slice in vitro was used for the research. The neuroprotective effects of ketamine on the OGD injury of rat hippocampal slices were assessed by 2,3,5 triphenyl tetrazolium chloride (TTC) staining. The changes of phospho p38 protein level in the hippocampus during ischemia reperfusion and the effects of ketamine on the phospho p38 protein activation were examined by Western blot. RESULTS : Ketamine significantly inhibited the decrease of OD in brain slices by TTC staining. The activation of phospho p38 protein increased after reperfusion 15 min, and it consistently expressed at 2 h. Ketamine (5 and 10 mol·L -1 ) markedly inhibited the activation of phospho p38 protein ( P < 0.05 ). Z CONCLUSION : Ketamine shows the neuroprotective effect related to the inhibition of activation of phospho p38 protein induced by oxygen glucose deprivation(OGD) in the rat hippocampal slices.

关 键 词：脑片 缺血再灌注 氯胺酮 P38 免疫印迹法 

分 类 号：R971.3[医药卫生—药品]