β片层阻断肽对AD模型小鼠学习记忆及PI3K/AKT信号通路的影响

Effect of β-sheet breaker peptide on learning and memory and PI3K/AKT signaling pathway in AD model mice

目的:观察β片层阻断肽H102对阿尔茨海默病(AD)模型小鼠学习记忆的影响,探讨其是否通过PI3K/AKT参与Aβ代谢。方法:(1)将APP/PS1双转基因小鼠随机分为模型组和H102给药组,设同月龄同背景的C57BL/6J为正常对照组。H102给药组采用鼻腔给药,5μL/d。通过Morris水迷宫检测不同组小鼠的空间记忆能力的改变。(2)采用免疫组化、RT-PCR及Western blot技术检测PI3K/AKT信号通路相关蛋白P85、p AKT的表达。结果:(1)Morris水迷宫检测显示H102给药组在定位航行实验以及空间探索实验均优于模型组,且具有统计学意义。(2)PI3K的m RNA在模型组中显著降低,在H102给药组水平显著增高;ITGB5的m RNA水平在模型组升高,在H102给药组中明显下调,在H102给药组和模型组之间有显著差异。(3)与模型组比较H102给药组PI3K(P85)与p AKT的表达量有明显升高。(4)PI3K和AKT免疫组化染色显示H102给药组的阳性细胞在大脑皮层和海马较模型组有显著增加。结论:H102通过激活PI3K/AKT信号通路,使胰岛素降解酶表达增加,进而加强了Aβ的降解,达到治疗AD的作用。

Objective： To observe the effects of H102 on the learming and memory ability in Alzheimer＇s disease mice and to explore the mechanism of H102 participating in Aβ metabolism. Methods： （1）The mice were randomly divided into normal group, model group and H102 group, and were treated with intranasal administrated, 5μL/d. Morris water maze test was used to record different changes in spatial memory of mice.（2）Immunohistochemistry was used to detect a specific protein, and RT-PCR and western blot to detect the expression of P85 and pAKT. Results： （1） Morris water maze test showed the H102 group in place navigation and spatial probe test was superior to the model group, with statistical significance. （2）The level of PI3K mRNA decreased significantly in the model group, with H102 group significantly higher;, ITGB5 mRNA levels were significantly lower in H102 group, and there were significant differences between the model and the H102 group.（3）Expression of PI3K （P85） and pAKT in H102 group had significantly increased as compare to the model group.（4） PI3K and AKT immunohistochemistry showed that positive staining cells in the cerebral cortex and hippocampus of H102 group were significantly increased compared with the model group. Conclusion： H 102 through the PI3K/AKT pathway of the insulin signaling pathway could increase the expression of IDE, which may further promote the endocytosis and degradation of Aβ in the brain, thus accelerating AI3 degradation, and enhancing therapeutic effect of AD treatment.