Abstract: Objective To study the effect of hesperetin early prevention on learning and memory ability and its mechanism related to TLR2 、NF-κB in Alzheimer's disease (AD) model mice. Methods Twelve 3-month-old C57/B6 mice were used as blank control group. 48 APP/PS1 double transgenic mice were randomly divided into four groups: model group, low dose group, middle dose group, high dose group (n=12 in each group). The low, middle and high dose groups were given hesperidin 20mg/kg, 40mg/kg and 80mg/kg respectively. The blank control group and the model group were given the same amount of carboxymethylcellulose sodium (each day for 6 months). The learning and memory ability was measured with Morris water maze. HE staining was used to observe the neuronal damage in CA1 region of hippocampus. Western blot was used to detect the contents of TLR2 and NF-κB protein in brain tissue of mice. Results Compared with the blank control group, the escaping latency of the model group was significantly prolonged, the times crossing the hidden platform was significantly decreased (P<0.05), and the neuronal damage in the hippocampal CA1 region was obviously increased. The contents of TLR2 and NF-κB protein were significantly increased (P<0.05). Compared with the model group, the escaping latency of mice in the low, middle and high dose groups was significantly shortened, the times crossing the hidden platform was significantly increased (P<0.05), and the neuronal damage in the hippocampal CA1 region was mild. The content of TLR2 and NF-κB protein decreased significantly (P<0.05). Conclusion Hesperetin early prevention can significantly improve the learning and memory ability and the injury of hippocampal neurons in APP/PS1dE9 mice, and its mechanism might be related to the down-regulation of TLR2 and NF-κB protein expression.

Key words: Alzheimer's disease, hesperidin, appswe/ps1de9, early intervention, TLR2, NF-κB;

摘要： 目的 研究橙皮素早期干预对APP/PS1小鼠学习记忆能力的影响与TLR2、NF-κB蛋白的表达。方法 12只3月龄C57/B6小鼠为空白对照组,48只APP/PS1双转基因小鼠随机分为模型组和橙皮素低、中、高剂量组,每组12只。低、中、高剂量组分别灌胃给予橙皮素20mg/kg、40mg/kg、80mg/kg,空白对照组及模型组灌胃等体积羧甲基纤维素钠（CMC）,日1次,连续6个月。采用Morris水迷宫检测各组小鼠记忆能力,HE染色法观察小鼠海马CA1区神经元损伤情况,Western blot法检测小鼠脑组织TLR2和NF-κB蛋白含量。结果 与空白对照组相比,模型组小鼠逃避潜伏期明显延长（P<0.05）,跨越隐匿平台的次数明显减少（P<0.05）,海马CA1区神经元损伤明显,TLR2和NF-κB蛋白含量升高（P<0.05）;与模型组相比,橙皮素低、中、高剂量组小鼠逃避潜伏期缩短（P<0.05）,跨越隐匿平台的次数增加（P<0.05）,海马CA1区神经元损伤较轻,TLR2和NF-κB蛋白含量降低（P <0.05）。结论 橙皮素早期干预可明显改善APP/PS1dE9小鼠的学习记忆能力和海马神经元的损伤情况,其机制可能与下调TLR2和NF-κB蛋白表达水平有关。

关键词: 阿尔茨海默病, 橙皮素, APPswe/PS1dE9, 早期干预, TLR2, NF-кB