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β片层阻断肽H102对PAP小鼠脑内ERK信号转导通路的影响

王冰艳1,孙凤仙1,林来祥1,徐淑梅2   

  1. 1. 天津医科大学第二医院麻醉科
    2. 天津医科大学基础医学院生理学教研室
  • 收稿日期:2014-03-25 修回日期:2014-05-23 出版日期:2014-07-15 发布日期:2014-07-15
  • 通讯作者: 王冰艳

The Effects ofβ-Sheet Breaker Peptide H102on ERK Signal Transduction Pathway in Brain of PAP Double Transgenic Mice

  • Received:2014-03-25 Revised:2014-05-23 Published:2014-07-15 Online:2014-07-15

摘要:

【摘要】目的 研究β片层阻断肽H102对PAP双转基因小鼠脑内ERK信号转导通路的激活作用。方法 将PAP双转基因小鼠随机分为模型组和给药组,每组10只,设同背景C57BL/6J小鼠为对照组。给药组每日鼻腔给予 H102溶液(5.8mg/kg)5µL,对照组、模型组每日鼻腔给予等体积H102空白辅料溶液。30d后行Morris水迷宫测试。之后采用免疫组化及免疫印迹技术观察小鼠脑组织内RAS、P-MEK及P-ERK蛋白的表达变化。结果(1)Morris水迷宫测试。模型组小鼠学习记忆能力较对照组显著降低,给药组较模型组显著提高(均P<0.05)。(2)免疫组化及免疫印迹检测结果。模型组脑内RAS、P-MEK及P-ERK表达较对照组显著降低,给药组蛋白表达较模型组显著增高(均P<0.01)。结论β片层阻断肽H102可激活PAP双转基因小鼠脑内ERK信号转导通路,增加神经细胞PAS、P MEK及P-ERK的含量,改善PAP小鼠学习记忆能力。

关键词: 阿尔茨海默病, 鼻腔给药, ERK信号转导通路, β片层阻断肽

Abstract:

[Abstract] Objective To investigate the activation ofβ-sheet breaker peptide H102on ERK signal transduction pathway in brain of PAP double transgenic mice.Methods PAP double transgenic mice were randomly divided into model group and H102treatment group (n=10for each group). A group of C57BL/6J mice with the same genetic background was served as controls. H102(5.8mg/kg)5µL was infused by intranasal administration to mice in H102treatment group, and equal volume of blank solution of H102(chitosan, BSA) was given to mice in control group and model group. The ability of spatial reference memory was tested by Morris water maze after30days of treatment. Then immunohistochemistry tests and Western blot technique were used to detect the content of RAS, P-MEK and P-ERK proteins in mouse brain.Results (1) The ability of learning and memory was significantly lower in model group than that of control group. The ability of learning and memory was significantly improved in treatment group than that in model group (P<0.05). (2) The contents of RAS, P MEK and P-ERK in mouse brain were significantly lower in model group than those of control group, and these protein ex? pressions were significantly increased in treatment group than those in model group (P<0.01).Conclusion β-sheet break? er peptide H102can activate ERK signal transduction pathway in brain of PAP double transgenic mice, increase PAS, P MEK and P-ERK levels in nerve cells, and improve the ability of learning and memory in PAP mice.

Key words: Alzheimer's disease, neuronal apoptosis, ERK signal transduction pathway, β-sheet breaker