白藜芦醇对APP/PS1双转基因小鼠学习记忆能力的改善作用

Improvement effects of resveratrol on the learning and memory abilities of double transgenic APP/PS1 mice

目的探讨白藜芦醇对APP/PS1双转基因小鼠学习记忆能力的改善作用。方法 50只小鼠随机分为模型组、多奈哌齐组(10 mg/kg)及白藜芦醇低、中、高剂量组(25、50、100 mg/kg),每组10只,10只C57BL/6小鼠作为对照组,各组灌胃给药40 d。Morris水迷宫定位航行实验和空间探索实验分别检测小鼠学习记忆能力,免疫荧光法检测小鼠海马区星形胶质细胞表达,RT-PCR法和ELISA法分别检测小鼠海马区IL-1β、IL-6、TNF-αmRNA表达和水平。结果与模型组比较,白藜芦醇组缩短逃避潜伏期,增加穿越平台次数和目标象限停留时间,降低星形胶质细胞表达及IL-1β、IL-6、TNF-αmRNA表达和水平,以中、高剂量组更显著(P<0. 05,P<0. 01)。结论白藜芦醇可改善APP/PS1双转基因小鼠学习记忆能力,其机制可能与抑制星形胶质细胞增生和炎性因子释放、减轻炎症反应有关。

AIM To explore the improvement effects of resveratrol on learning and memory abilities of double transgenic APP/PS1 mice.METHODS Fifty mice randomly assigned into model group,donepezil group(10 mg/kg)and resveratrol low-dose,medium-dose,high-dose groups(25,50,100 mg/kg),ten mice in each group,were intragastrically administered with the corresponding agents for 40 d,and ten C57BL/6 mice were recruited into control group.Mouse learning and memory activities were detected by Morris water maze place navigation test and spatial probe test,respectively.Astrocyte expression in mouse hippocampal area was detected by immunofluorescence.IL-1β,IL-6,TNF-αmRNA expressions and levels in mouse hippocampal area were determined by RT-PCR and ELISA,respectively.RESULTS Compared with the model group,the resveratrol groups demonstrated shortened escape latent period,increased platform-crossing frequency and target quadrant residence time,decreased astrocyte expression and IL-1β,IL-6,TNF-αmRNA expressions and levels,especially for the mediumdose,high-dose groups(P<0.05,P<0.01).CONCLUSION Resveratrol can improve the learning and memory abilities of double transgenic APP/PS1 mice,whose mechanisms may contribute to inhibiting astrocyte hyperplasia and inflammatory factor release,and alleviating inflammatory reactions.