中文摘要：

目的探讨侧脑室单次注射Forskolin后，大鼠海马组织中tau蛋白异常磷酸化和记忆障碍持续时间及两者关系。方法向大鼠侧脑室内单次注射80μmol／L的cAMP-依赖性蛋白激酶A（PKA）激动剂-Forskolin 40μl，用特定抗体通过免疫印迹和免疫组织化学方法检测大鼠海马tau蛋白磷酸化水平的改变，同时用Morris水迷宫法检测大鼠空间记忆能力。结果侧脑室注射Forskolin后，大鼠海马tau蛋白磷酸化水平在24、48和72h均有显著升高（P〈0．05），在48h达到高峰（P〈0．01），在72h呈恢复趋势；大鼠在注射后24、48和72h均有空间记忆障碍（P〈0．05），这种记忆障碍在48h最明显（P〈0．01），在72h时亦呈明显恢复趋势；大鼠空间记忆保留障碍与海马tau蛋白PHF-1位点的磷酸化程度呈正相关（r=0．97，P〈0．05），与Tau-1位点的非磷酸化程度呈负相关（r=-0．963，P〈0．05），与pS214位点的磷酸化程度无相关性（r=0．705，P〉0．05）。结论大鼠侧脑室单次注射Forskolin只在一定时间内引起tau蛋白异常磷酸化和动物记忆障碍，且二者的改变趋势存在一定相关性。

英文摘要：

Objective To investigate the duration of tau hyperphosphorylation and spatial memory retentive deficit induced by single injecting with Forskolin, a protein kinase A activator, into lateral ventricle of rats, and the correlation between the two pathological alterations. Methods Forskolin （80 μmoL/L, 40 μl） was injected into the lateral ventricle by stereotaxic injection. Tau phosphorylation and spatial memory retention were measured by Western blot/immunocytochemistry and Morris-Water-Maze test, respectively. Results The phosphorylation levels of tan at Tau-1, PHF-1, and pS214 epitopes were significantly elevated at 24, 48 and 72 h after single administration of Forskolin （ P 〈 0. 05 ）. The most significant elevation was seen at 48 h （P 〈 0. 01 ） and it tended to recover at 72 h （ P 〈 0. 05 ） after injection. The correlation between the two pathological alterations was positive at PHF-1 site （r =0.97, P 〈0.05）, negative at Tan-1 site （r= -0.963, P 〈0.05）, and not significant at pS214 site （r =0. 705, P 〉0. 05）. Condusions Forskolin can induce tan hyperphosphorylation and spatial memory retentive deficit within a certain period of time. The level of tan phosphorylation in hippocampus is somehow correlated with the spatial memory deficit in rats.