葛根素减轻APP／PS1双转基因小鼠的认知障碍和tau蛋白过磷酸化

葛根素减轻葛根素减轻APPAPP／／PS1PS1双转基因小鼠的认知障碍和双转基因小鼠的认知障碍和tautau蛋白过磷酸化蛋白过磷酸化 该实验利用 APP/PS1 双转基因模型小鼠，观察葛根素对小鼠学习记忆能力 及 tau 蛋白磷酸化的影响。选用 APP/PS1 双转基因模型小鼠，3 个月龄后开始灌 胃给药。给药3 个月后，通过Morris 水迷宫实验测试小鼠学习记忆能力的变化； 行为学测试结束后，处死动物，留取脑组织标本，ELISA 法检测皮层 Aβ 水平； Western blot法检测皮层tau蛋白、 磷酸化tau蛋白、 GSK3β及磷酸化GSK3β （Ser9） 蛋白表达情况。Morris 水迷宫实验显示，APP/PS1 双转基因模型小鼠逃避潜伏期 较正常对照组明显延长，原象限停留时间明显缩短。葛根素组小鼠逃避潜伏期较 模型组明显缩短，原象限停留时间明显延长。与正常对照组比较 APP/PS1 双转 基因模型小鼠皮层 Aβ 水平增多，磷酸化 tau 蛋白表达显著增加，磷酸化 GSK3β （Ser9）蛋白表达降低；给予葛根素后，APP/PS1 转基因小鼠寻台潜伏期明显缩 短，Aβ 水平减少，磷酸化 tau 蛋白表达显著减少，磷酸化 GSK3β（Ser9）蛋白 表达增加。葛根素通过减少Aβ 的生成，激活 GSK3β 信号通路，抑制 tau 蛋白磷 酸化，改善 APP/PS1 双转基因模型小鼠的学习记忆损害。 标签 葛根素；阿尔茨海默病；tau 蛋白；GSK3β；β-淀粉样蛋白 [Abstract] To observe the effect of puerarin on learning and memory function and tau phosphorylation in APP/PS1 transgenic mice ， drugs were administered to 3-month old APP/PS1 transgenic mice. Learning and memory function of mice were assessed by Morris water maze test 3 months after treatment. Animals were decapitated after behavioral test. The levels of Aβ were detected by ELISA， the expression of protein [tau，phosphorylated tau，GSK3β and p-GSK3β （Ser9） ] were assessed by Western blot. Morris water maze test showed that the escape latency of APP/PS1 double transgenic mice was significantly longer than that of the normal control group， and the residence time of the original quadrant was significantly shorter. The escape latency of puerarin group was significantly shorter and the residence time of the original quadrant was prolonged compared with the model group. Compared with the normal control group， the levels of Aβ in the cortex of APP/PS1 transgenic mice were increased，the expression of phosphorylated tau was significantly increased，and the expression of phosphorylated GSK3β （Ser9）protein was decreased. Treatment with puerarin， the latency of APP/PS1 transgenic mice was significantly reduced， the level of Aβ was decreased， the expression of phosphorylatedtauwassignificantlydecreased ，andtheexpressionof phosphorylated GSK3β （Ser9）protein was increased. Puerarin improves the learning and memory impairment by reducing the ation of Aβ， activating the GSK3β signaling pathway， inhibiting the phosphorylation of tau in APP/PS1 double transgenic mice. [Key words] puerarin；Alzheimer′s disease；tau protein；GSK3β； amyloid-beta protein