Effect of β-sheet breaker peptide on learning and memory and PI3K /AKT? signaling pathway in AD model mice
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; APP/PS1 transgene mice; morris water maze; PI3K/AKT signaling pathway; Alzheimer; s diseea目的:观察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给药组,设同月龄同背景的C57BL/6J为正常对照组。采用鼻腔给药,5 μL/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AKT/PI3K信号通路相关蛋白P85、pAKT的表达。结果:(1)Morris水迷宫检测显示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mRNA在模型组中显著降低,H102给药组水平显著增高;ITGB5的mRNA水平在模型组升高,H102给药组中有明显下调,H102给药和模型组之间有显著差异。(3)PI3K(P85)与pAKT的表达量与模型组比较H102组有明显升高。(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IDE表达增加,进而加强了Aβ的降解,达到治疗AD的作用。
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Objective: To observe the effects of H102, behavioral studies, semi-quantitative detection of DNA and protein and to investigate H102 mechanism involved in Aβ. Methods: (1)The mice were randomly divided into normal group, control group and H102 group. And were treated with intranasal administrated, 5 μL/ d. Morris water maze test was used to record different changes in spatial memory of mice.(2)We use immunohistochemistry 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 treatment group significantly higher; mRNA levels were significantly lower in ITGB5 H102 group, and there were significant differences between the control and the H102 group.(3)Expression of PI3K (P85) and pAKT in H102 group had significantly increased as compare to the control group.(4)PI3K and AKT immunohistochemistry showed positive staining cells H102 group in the cerebral cortex and hippocampus were significantly increased. Conclusion: H102 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 Aβ degradation, and enhancing therapeutic effect of AD treatment.
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LI Jing,FU Xue-fei,SUN Feng-xian,et al.Effects of β-sheet breaker peptide H102 on LPL and PPAR-γ protein in double transgenic AD mice[J].Journal of Tianjin Medical University,2016,22(05):396.