摘要
背景和目的:中风是导致死亡和残疾的主要原因,以神经元死亡为特征,可由血流减少或中断引起。本研究评价了肾素-血管紧张素系统的一种新肽阿拉曼定在体外和体内脑缺血模型中的作用。 方法:在体外模型中,将雄性C57/Bl6小鼠的海马切片置于无糖aCSF溶液中,用95%n2和5%二氧化碳起泡模拟脑缺血。生成阿拉曼定浓度-反应曲线来评估细胞损伤、谷氨酸能兴奋性毒性和细胞死亡。在体内模型中,SD大鼠通过双侧颈总动脉闭塞(BCCAo未处理)诱导大鼠脑缺血/再灌注。在BCCAo术前20-30min给予侧脑室内注射阿拉曼定。BCCAo后24h和72h进行神经学试验。在BCCAo术后72h,检测脑内细胞因子水平、氧化应激标志物和免疫荧光水平。 结果:阿拉曼定能保护脑片免受细胞损伤、兴奋性毒性和细胞死亡。当阿拉曼丁呤受体被阻断时,保护作用就消失了。ICV注射阿拉曼定可减轻BCCAo组动物的神经功能缺损,并减少凋亡神经元/细胞的数量。此外,阿拉曼定在BCCAO动物中诱导了抗炎作用,通过降低大脑中SOD、过氧化氢酶和GSH活性来降低TNFα、IL1β、IL-6和抗氧化作用。 结论:本研究首次显示阿拉曼定在不同缺血性卒中模型中具有神经保护作用。
关键词: 肾素-血管紧张素系统,氧化应激,脑缺血,OGD,ICV,细胞因子,神经功能缺陷。
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