雌激素膜受体诱导大鼠海马CA1区AKT快速激活及其抗缺血性神经元损伤作用  

Neuroprotective role induced by destrogen receptor via up-regulation Akt phosphorylation against ischemic injury in hippocampal CA1 region of the rats

作　　者：杨丽彩[1] 王瑞敏[1] 周彩凤[1] 田炜[1] 赵小平[1] 杨方[1] 

机构地区：[1]华北煤炭医学院实验研究中心,河北唐山063000

出　　处：《电子显微学报》2009年第6期562-566,共5页Journal of Chinese Electron Microscopy Society

基　　金：国家自然科学基金资助项目(No.30970664);河北省自然科学基金资助项目(No.C2008000997);河北省教育厅自然科学基金资助项目(No.2008140)~~

摘　　要：目的:使用结合雌激素EDC研究雌激素对缺血性神经元的保护作用及其可能的分子机制。方法:SD雌性大鼠行双侧卵巢切除术,一周后制作四动脉结扎全脑缺血模型。实验动物随机分为sham组、缺血再灌注组、给药组(脑室注射EDC、ICI182,780、Ly294,002)和溶剂对照组。采用激光扫描共聚焦显微镜技术观察EDC在海马CA1区神经元中的亚细胞定位,观察其对缺血后神经元损伤的影响和p-AKT免疫活性的变化。结果:给予FITC-EDC1h后,EDC定位于海马CA1区神经元胞膜,并明显降低了再灌注7d诱导的神经元损伤;脑缺血再灌注10min,EDC组p-Akt蛋白水平较缺血再灌组和溶剂对照组明显升高;EDC的神经保护作用及其对AKT磷酸化激活的诱导均被ICI182,780和Ly294,002显著抑制。结论:雌激素膜受体诱导AKT的快速激活是雌激素神经保护作用的重要机制。Objective：To study the neuroprotective role of estrogen-dendrimer conjugates（EDC）,indcuced by estrogen receptor and further to clarify the possible mechanism following cerebral ischemia in hippocampal CA1 region of the rats.Methods：Adult Sprague Dawley female rats were bilaterally ovariectomized,and 1 week later cerebral ischemia was induced by four-vessel occlusion.Experimental animals were randomly divided into four groups,sham,ischemia-reperfusion,drug-treated and vehicle groups.EDC,AKT inhibitor ly294,002,estrogen receptor（ERs）antagonist ICI182,780 were injected intracerebroventricularly into the right lateral ventricle.Immunofluorescence was used to observe the location of EDC,neuron survival and the level of AKT phosphorylation in hippocampal CA1 region of the rats.Results：EDC distributed in the neuronal membrane of hippocampal CA1 region at 1 h after administrating EDC-FITC and significantly reduced the delayed neuronal injury induced by 7 d reperfusion after 10 min ischemia.Compared with vehicle groups,EDC rapidly enhanced the level of AKT phosphorylation at 10 min of reperfusion.Either the neuroprotection role of EDC or the increase of p-AKT was markedly prevented by ly294,002 and ICI182,780.Conclusion：Rapid activation of Akt induced by EDC through estrogen mebrance receptor might atribute to neuroprotection role of estrogen against ischemic insult in hippocampal CA1 region of the rats.

关 键 词：脑缺血再灌注 雌激素受体 EDC AKT 

分 类 号：R741[医药卫生—神经病学与精神病学]