CREB1 对血管性痴呆大鼠认知功能障碍的 影响及机制研究

Effect of CREB1 on cognitive dysfunction in rats with vascular dementia and its mechanism

摘要:

目的 探讨环腺苷酸反应成分结合蛋白1（CREB1）对血管性痴呆大鼠认知功能障碍的影响及 机制研究。方法 将40 只大鼠根据随机数字表法分为对照组、模型组、阴性对照组及CREB1 过表达组，每 组10 只。采用四血管阻断法复制血管性痴呆模型，采用水迷宫实验和旷场实验测定大鼠的认知功能，Western blotting 测定海马组织CREB1、Caspase-3、Bcl-2、Bax、磷脂酰肌醇3 激酶（PI3K）、磷酸化蛋白激酶B（p-PKB） 及蛋白激酶B（PKB）蛋白水平。结果 与对照组比较，模型组、阴性对照组及CREB1 过表达组大鼠旷场实 验活动次数减少，活动距离缩短（P <0.05），逃避潜伏期延长（P <0.05），穿越原平台次数减少（P <0.05）；海 马组织Bcl-2、PI3K 及p-PKB 蛋白水平降低（P <0.05），海马组织Caspase-3、Bax 蛋白水平升高（P <0.05）； 与模型组和阴性对照组比较，CREB1 过表达组大鼠旷场实验活动次数增加，活动距离延长（P <0.05），逃 避潜伏期缩短（P <0.05），穿越原平台次数增加（P <0.05）；海马组织CREB1、Bcl-2、PI3K 及p-PKB 蛋 白水平升高（P <0.05），海马组织Caspase-3、Bax 蛋白水平降低（P <0.05）。结论 血管性痴呆大鼠脑组织 CREB1 水平降低，过表达CREB1 可通过激活PI3K/PKB 信号通路，抑制海马神经细胞凋亡，改善血管性痴 呆大鼠的认知功能。

Abstract:

Objective To investigate the effect of cyclic adenosine monophosphate receptor binding protein 1 (CREB1) on cognitive dysfunction in rats with vascular dementia and its possible mechanism. Methods A total of 40 rats were divided into control group, model group, negative control group and CREB1 overexpression group according to random number method, 10 rats in each group. The vascular dementia model was established by using the four-vessel blockade method. The water maze test and the open field test were used to determine the cognitive function of rats. Western blotting analysis was used to determine the levels of hippocampal tissue CREB1, aspartate proteolytic enzyme-3 (Caspase-3), B lymphocyte tumor-2 gene (Bcl-2), Bcl-2 related X protein (Bax), phosphatidylinositol-3-kinase (PI3K), phosphorylated protein kinase B (p-PKB) and PKB protein. Results Compared with the control group, the number of experimental activities and the distance of activity were decreased (P < 0.05),the escape latency was increased (P < 0.05), the number of crossing the original platform was decreased. (P < 0.05), the levels of CREB1, Bcl-2, PI3K and p-PKB protein in hippocampus were decreased (P < 0.05) and the levels of Caspase-3 and Bax in hippocampus were increased (P < 0.05) in the model group, the negative control group and the CREB1 overexpression group. Compared with the model group and the negative control group, the number of experimental activities and the distance of activity were increased (P < 0.05), the escape latency were decreased (P < 0.05), the number of crossing the original platform were increased (P < 0.05), the levels of CREB1, Bcl-2, PI3K and p-PKB in hippocampus were increased (P < 0.05) and the levels of Caspase-3 and Bax in hippocampus were decreased (P < 0.05) in the CREB1 overexpression group. Conclusions The level of CREB1 in brain tissue of rats with vascular dementia is decreased. Overexpression of CREB1 can ameliorate the cognitive function of vascular dementia rats by activating PI3K/PKB signaling pathway to inhibit hippocampal neuronal apoptosis.