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

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。

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

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 ly294,0...