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中国应用生理学杂志 ›› 2016, Vol. 32 ›› Issue (4): 293-298.doi: 10.13459/j.cnki.cjap.2016.04.002

• 研究论文 • 上一篇    下一篇

β片层阻断肽H102对双转基因AD小鼠突触可塑性相关蛋白的影响

袁小涌, 王超, 孙凤仙, 徐淑梅   

  1. 天津医科大学生理学教研室, 天津 300070
  • 收稿日期:2016-01-08 修回日期:2016-03-04 出版日期:2016-07-28 发布日期:2018-06-20
  • 通讯作者: 徐淑梅,Tel:13012268139;E-mail:xushm@tijmu.edu.cn E-mail:xushm@tijmu.edu.cn
  • 基金资助:
    国家科技重大专项基金资助(2009ZX09103029);天津市科技支撑重点项目基金资助(09ZCKFSH00100)

Effects of β-sheet breaker peptide H102 on synaptic plasticity associated proteins in double transgenic AD mice

YUAN Xiao-yong, WANG Chao, SUN Feng-xian, XU Shu-mei   

  1. Department of Physiology, Tianjin Medical University, Tianjin 300070, China
  • Received:2016-01-08 Revised:2016-03-04 Online:2016-07-28 Published:2018-06-20
  • Supported by:
    国家科技重大专项基金资助(2009ZX09103029);天津市科技支撑重点项目基金资助(09ZCKFSH00100)

摘要: 目的:观察β片层阻断肽H102对双转基因AD小鼠突触可塑性相关蛋白表达及学习记忆能力的影响,探讨H102的作用机制。方法:选用8周龄APPswe/PS1dE9双转基因雄性小鼠30只,随机选取15只小鼠设为模型组,剩下15只小鼠设为给药组;对照组选用15只同周龄同背景C57BL/6J小鼠。给药组每日经鼻腔给予H102溶液(5.8 mg/kg)5μl,对照组和模型组每日经鼻腔给予辅料溶液5μl。给药16周后,采用Morris水迷宫法检测双转基因AD小鼠空间学习记忆能力的变化,采用免疫组织化学方法和Western blot实验技术测定β-淀粉样蛋白1-42(Aβ1-42)和突触可塑性相关蛋白磷酸化蛋白激酶C亚型α、β2、γ(p-PKCα、p-PKCβ2、p-PKCγ)、磷酸化离子型谷氨酸受体1(p-NMDAR1)、磷酸化钙/钙调素依赖蛋白激酶α(p-CaMKⅡα)和磷酸化环腺苷酸应答元件结合蛋白(p-CREB)在小鼠脑中的表达水平。结果:Morris水迷宫检测结果表明H102能明显提高双转基因AD小鼠的空间学习记忆的能力。免疫组织化学和Western blot技术检测表明H102能明显减少双转基因AD小鼠脑内Aβ1-42蛋白的表达,H102能明显提高双转基因AD小鼠脑内突触可塑性相关蛋白p-PKCα、p-PKCβ2、p-PKCγ、p-NMDAR1、p-CaMKⅡα和p-CREB的表达。结论:β片层阻断肽H102能提高双转基因AD小鼠的突触可塑性,提高双转基因AD小鼠的学习记忆能力。

关键词: H102, APP/PS1双转基因小鼠, Morris水迷宫, 1-42

Abstract: Objective:To investigate the effects ofβ-sheet breaker peptide H102 on expression of synaptic plasticity associated proteins and learning and memory functions in double transgenic Alzheimer's disease(AD) mice,and to discuss its mechanisms. Methods:Thirty APP-swe/PS1dE9 double transgenic male mice of 8 weeks were randomly divided into model group and H102 treatment group (15 mice per group). In addition,a group of C57BL/6J mice with the same age and background was set as normal. H102 (5.8 mg/kg) 5 μl was infused by in-tranasal administration to mice in H102 treatment group,and equal volume of blank solution of H102 (chitosan,BSA) was given to mice in con-trol group and model group. The ability of spatial reference memory was tested by Morris Water Maze after 16 weeks treatment,then immunohis-tochemistry tests and Western blot technique were used to detect the content ofβ-amyloid peptide(Aβ1-42) protein and phospho protein kinase C α、β2、γ(p-PKCα, p-PKCβ2, p-PKCγ), phospho-N-methyl-D-aspartate receptor1(p-NMDAR1), phospho-Calcium/Calmodulin dependent pro-tein kinaseⅡα(p-CaMKⅡα) and phospho-cAMP response element binding protein(p-CREB) of synaptic plasticity associated proteins in mice brain. Results:The ability of learning and memory was significantly improved in H102 treatment group than that in model group by the test of Morris Water Maze. The contents of Aβ1-42 proteins and p-PKCα, p-PKCβ2, p-PKCγ, p-NMDAR1, p-CaMKⅡαand p-CREB of synaptic plas-ticity associated proteins in mice brain were improved significantly in H102 treatment group than those in model group by the test of immunohis-tochemistry tests and Western blot technique. Conclusion:β-sheet breaker peptide H102 can significantly improve synaptic plasticity and the ability of learning and memory in double transgenic AD mice.

Key words: H102, APP/PS1 double transgenic mice, Morris Water Maze, 1-42

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