[Gly14]-humanin拮抗Aβ_(31-35)引起的大鼠空间学习记忆损伤  

[Gly14]-humanin protects against Aβ_(31-35)-induced impairment of spatial learning and memory in rats

作　　者：原丽[1] 韩维娜[1] 李少凤[1] 刘晓杰[1] 武美娜[1] 祁金顺[1] 

机构地区：[1]山西医科大学生理学系,太原030001

出　　处：《生理学报》2012年第6期625-632,共8页Acta Physiologica Sinica

基　　金：supported by the Special Foundation for High Schools Doctoral Program of Ministry of Education;China (No.20101417110001);the Scientific Research Foundation for the Returned Overseas Chinese Scholars in Shanxi Province;China (No.2010-51);the Natural Science Foundation of Shanxi Province of China (No.2010011049-3);Science and Technology Fund of Taiyuan Municipality (No.201010-1400);Scientific and Technologial Innovation Programs of Higher Education Institutions in Shanxi Province;China (No.20091111)

摘　　要：淀粉样β蛋白(Amyloid β protein,Aβ)与阿尔茨海默病(Alzheimer’s disease,AD)发病机理密切相关,拮抗Aβ神经毒性或清除脑内沉积的Aβ已成为一个主要的AD治疗策略。本研究采用Morris水迷宫技术,探讨了海马内注射Aβ31-35对大鼠空间学习记忆行为的影响,并在此基础上研究了[Gly14]-humanin(HNG)拮抗Aβ的神经保护作用及其可能机制。结果显示,双侧海马注射2.0nmol的Aβ31-35后,大鼠定位航行试验中寻找水下平台的平均逃避距离较对照组明显延长;撤除平台后空间探索试验中目标象限内的游泳距离占游泳总距离的百分比明显下降;HNG(0.2和2.0nmol)预处理拮抗了Aβ31-35所致的逃避距离延长和游泳距离百分比下降;给予酪氨酸激酶抑制剂Genistein(40nmol)则几乎完全阻断HNG的抗Aβ效应。以上结果表明,HNG可以剂量依赖性保护大鼠的空间学习记忆免受Aβ伤害,其机制可能与激活内源性酪氨酸激酶途径有关,提示HNG上调酪氨酸激酶信号转导对AD患者认知功能的改善具有重要意义。Amyloid β protein （Aβ） is closely involved in the pathogenesis of Alzheimer’s disease （AD）, and one of the main strategies for AD treatment is antagonizing the neurotoxicity of Aβ or even clearing the Aβ deposited in the brain. The present study was aimed to observe the effects of intrahippocampal injection of Aβ31-35 on the spatial learning and memory of rats by using Morris water maze technique, and explore the neuroprotective effects and possible mechanism of [Gly14]-humanin （HNG） against Aβ-induced deficits in learning behavior. The results showed that bilateral intrahippocampal injection of 2.0 nmol Aβ31-35 significantly increased the mean traveled distance of rats in searching for the hidden underwater platform and decreased the distance percentage in the target quadrant in probe test after withdrawal of platform, whereas pretreatment with HNG （0.2 nmol and 2.0 nmol） suppressed Aβ31-35-induced increase in the traveled distance and decrease in swimming distance percentage. Application of Genistein （40 nmol）, a specific tyrosine kinase inhibitor, almost completely blocked the antagonistic effects of HNG against Aβ31-35 . These results indicate that HNG can dosedependently prevent against Aβ31-35-induced impairment in spatial learning and memory of rats, and the neuroprotective effects of HNG might involve the activation of endogenous tyrosine kinase pathway, suggesting that up-regulation of the tyrosine kinase signaling by using HNG might be of great significance for the improvement of cognitive function in AD.

关 键 词：[Gly14]-humanin Aβ31-35 MORRIS水迷宫 空间学习记忆 

分 类 号：R749.16[医药卫生—神经病学与精神病学]