反复双侧颈总动脉闭塞小鼠海马Akt和糖原合成酶激酶-3β表达  

Expressiom of Akt and glycogen synthasekinase-3β in the hippocampus after repetitive bilateral common carotid artery occlusion in nice

作　　者：范鸣玥[1] 郭艳苏[2] 孟笑梅[3] 李玲[1] 董艳红[1] 崔文柱[1] 吕佩源[1] 

机构地区：[1]河北省人民医院神经内科,石家庄050051 [2]河北医科大学第二医院神经内科,河北省神经病学重点实验室,石家庄050000 [3]河北省人民医院图书馆,石家庄050051

出　　处：《国际脑血管病杂志》2012年第8期583-588,共6页International Journal of Cerebrovascular Diseases

基　　金：基金项目：河北省自然科学基金（C2009001483）;国家留学人员科技活动择优资助项目（人力资源与社会保障部2009-11-6）

摘　　要：目的探讨反复双侧颈总动脉闭塞所致血管性痴呆（vasculardementia，VaD）小鼠海马Akt和糖原合成酶激酶-3β（gtycogensynthasekinase-3β，GSK3β）蛋白表达。方法48只健康雄性C5781／6小鼠随机分为正常组、假手术组和模型组，每组16只。模型组采用反复3次间断阻断双侧颈总动脉建立小鼠VaD模型，假手术组只分离双侧颈总动脉但不阻断，正常组不接受任何处理。术后4周利用水迷宫实验和跳台实验观测各组小鼠行为学改变，采用HE染色观察海马组织病理学变化，采用蛋白质印迹法检测海马Akt、P．Akt（Ser473）、GSK3p、p-GSK3p（Set9）蛋白表达。结果水迷宫实验中，模型组学习阶段和记忆阶段游完全程时间延长（学习阶段：F=19．389，P〈0．05；记忆阶段：F=27．929，P〈0．05），错误次数增加（学习阶段：F=7．228，P〈0．05；记忆阶段：F=21．189，P〈0．05）；跳台实验中，模型组小鼠学习阶段反应时间延长（F=19．162，P〈0．05）、错误次数增加（F=6．562，P〈0．05），记忆阶段潜伏时间缩短（F=10．634，P〈0．05）、错误次数增加（F=12．890，P〈0．05）。同时，HE染色显示模型组海马CA1区神经元减少，神经胶质细胞增生；p-Akt（Ser473）（F=37．849，P〈0．05）和P—GSK3β（Set9）（F=67．725，P〈0．05）蛋白表达在术后4周较假手术组显著上调，而各组间Akt（F=1．004，P〉0．05）和GSK3β（F=0．329，P〉0．05）总蛋白表达无显著差异。结论反复双侧颈总动脉闭塞可造成小鼠学习记忆障碍，海马组织受损严重。磷酸化Akt和GSK3β表达可能参与了VaD的机制。Objective To investigate the expressions of protein kinase B （PKB/Akt） and glycogen synthase kinase-3β in the hippocampus in mice with vassar dengntia （VaD） induced by repetitive bilateral common carotid artery occlusion. Methods Forty-eight healthy adult male C57B1/6 mice were randomly allocated into 3 group： normal group, sham operation group, and model group （n = 16 in each group）. A mouse VaD model was induced by intermittent blocking the bilateral common carotid artery for 3 times in the model group. The sham group only separated the bilateral common carotid artery, but did not block it. The normal group did not receive any treatment. The behavioral changes of the mice were observed using the water maze and step-down tests at 4 weeks after procedure. HE staining was used to observe the bistopathological changesof hippocampal tissue. The Westem blotting was used to detect the expressions of Akt, p-Akt （Ser473）, GSK3β and p-GSK3β （Ser9） proteins. Results In the water maze test, the time of swimming the entire distance was prolonged at the learning stage and memory stage （learning stage： F = 19. 389, P 〈0. 05; memory stage： F = 27. 929, P〈0. 05）, the number of errors increased （learning stage： F=7. 228, P〈0. 05; memory stage： F= 21. 189, P 〈0. 05） in the model group. In the step-down test, the response time was prolonged （F = 19. 162, P 〈0. 05） at learning stage and the number of errors increased （F = 6. 562, P 〈 0. 05）, the latency time was shortened （F = 10. 634, P 〈 0. 05） and the number of errors increased （F = 12. 890, P 〈 0. 05） in the model group. At the same time, HE staining showed the reduction of neurons and the proliferation of glial cells in the hippocampal CA1 region in the model group; p-Akt （Ser473） （F = 37. 849, P 〈 0. 05） and p-GSK3[3 （Ser9） （F =67. 725, P 〈0. 05） protein expressions were up-regulated sigtificantly （F =37. 849, P 〈0. 05; F =67. 725, P 〈0. 05） at 4 weeks after procedure compared

关 键 词：原癌基因蛋白质c—akt 糖原合酶激酶3 痴呆 血管性 脑缺血 海马(脑) 疾病模型 动物 小鼠 

分 类 号：R285.5[医药卫生—中药学]