新橙皮对小鼠学习记忆功能保护.docVIP

新橙皮苷对APP/PS1双转基因小鼠学习记忆能力的保护作用 及其机制研究 李平，张赛，张巧莲，李双英 武警后勤学院附属医院脑科医院神经内科 天津 300162 摘 要： 目的 考察新橙皮苷对APP/PS1双转基因小鼠学习记忆的影响并探究其可能的分子机制。方法 将3月龄的APP/PS1双转基因小鼠随机分为4组，分别为模型组、新橙皮苷高、中、低剂量组，并选取同月龄同背景的C57BL/6J小鼠作为正常对照组。各治疗组每天灌胃给药1次，连续灌胃3个月。应用水迷宫实验和被动穿梭实验检测APP/PS1双转基因小鼠的学习记忆能力，应用ELISA检测海马组织TNF-α和IL-6的水平和NF-κB活力，应用Western blot检测海马组织RAGE和细胞核内NF-κB/p65表达的变化。结果 与C57BL/6J小鼠相比，APP/PS1双转基因小鼠在水迷宫实验中潜伏期显著延长（P ＜0.01），穿越平台次数显著减少（P ＜0.01），在被动穿梭实验潜伏期显著缩短（P ＜0.01），错误次数显著增加（P ＜0.01）。而海马组织TNF-α和IL-6的水平，NF-κB活力，RAGE和细胞核内NF-κB表达均显著上调（P ＜0.01）。而新橙皮苷各剂量组能够显著缩短APP/PS1双转基因小鼠在水迷宫实验中潜伏期 （P ＜0.01），增加穿越平台次数 （P ＜0.01），延长APP/PS1双转基因小鼠在被动穿梭实验潜伏期 （P ＜0.01），减少错误次数 （P ＜0.01）。海马组织TNF-α和IL-6的水平，NF-κB活力，RAGE和细胞核内NF-κB/p65表达均显著下调（P ＜0.01）。结论 新橙皮苷能够抑制APP/PS1双转基因小鼠海马组织的RAGE和细胞核内NF-κB的蛋白表达，抑制TNF-α和IL-6水平，改善APP/PS1双转基因小鼠的学习记忆能力。 关键词 阿尔兹海默病；新橙皮苷；APP/PS1双转基因小鼠；NF-Κb 中图分类号：R741.05 Neohesperidin attenuates learning and memory deficits in APP/PS1 mice through suppression of RAGE/NF-κB signaling Abstract; Object To investigate the protective effects and underlying mechanism of NH on learning and memory deficits in APP/PS1 mice. Methods The 3 month aged mice were randomly assigned to 4 groups, i.e., the APP/PS1 group, the high dosage of NH (80 mg?kg-1), the middle dosage of NH (40 mg?kg-1) and the low dosage of NH (20 mg?kg-1). The nontransgenic littermates were used as control group. For the NH+APP/PS1 group, NH was daily intragastric administeration to mice for 3 months. For the control and APP/PS1 groups, the mice were given the same amount of saline. The learning and memory capabilities of APP/PS1 mice were determined by Morris water maze and step-through positive avoidance tests. The levels of TNF-αand IL-6 and the activity of NF-κB in hippocampus were detected by ELISA. The protein expression of RAGE in hippocampus and nuclear NF-κB were determined by Western blot. Results Intragastric administration of NH for 90 days significantly improved the learning and memory capabilities of APP/PS1 mice. NH could reduce the activ