CD147对阿尔茨海默病模型大鼠学习记忆能力的干预作用

摘要

目的 探讨细胞外基质金属蛋白酶诱导因子(CD147)对阿尔茨海默病模型大鼠学习记忆能力的干预作用.方法 健康Sprague-Dawley大鼠按随机数字表法分为假手术组、模型组和CD147组,每组20只.所有大鼠10％水合氯醛(0.3 g/kg)腹腔注射麻醉,模型组和CD147组大鼠于双侧海马CA1区注入10μg的Aβ1～40,假手术组大鼠于同一部位注射等量的生理盐水.术后48 h,CD147组大鼠于双侧脑室注射CD147 cDNA,模型组和假手术组大鼠于同一部位注射等量生理盐水.采用Morris水迷宫实验对各组大鼠的学习记忆能力进行测试.采用蛋白印迹法检测β-淀粉样蛋白(Aβ)和γ-分泌酶表达.结果 从第3天开始,模型组大鼠逃避潜伏期时间较假手术组延长,而CD147组较模型组减少,差异均有统计学意义(P<0.05).模型组大鼠经过平台次数和经平台停留时间较假手术组减少,而CD147组较模型组均增加,差异有统计学意义(P<0.05).模型组大鼠脑组织Aβ和γ-分泌酶表达较假手术组增加,而CD147组较模型组大鼠减少,差异有统计学意义(P<0.05).结论 外源性CD147能够显著改善AD模型大鼠学习记忆能力,其具体机制可能与调节γ-分泌酶活性和下调Aβ的表达有关.%Objective To investigate the intervention effect of CD147 on learning and memory ability in rat model of Alzheimer's disease. Methods A total of 60 healthy Sprague-Dawley rats were randomly divided into sham operation group, model group and CD147 group, 20 rats in each group. All of the rats were anesthetized with intraperitoneal injection of 10％chloral hydrate (0.3 g/kg). The rats in the model group and the CD147 group were injected with Aβ1-40 (10μg) in the bilateral hippocampal CA1 regions, while the rats in the sham operation group were injected with the same amount of saline at the same sites. After 48 h, the rats in CD147 group were injected with CD147 cDNA in the bilateral ventricles, while the rats in model group and sham operation group were injected the same amount of saline at the same sites. Morris water maze test was used to detect the ability of learning and memory of rats. The expressions ofβamyloid protein (Aβ) andγ-secretase were detected by Western blot assay. Results The escape latency was significantly longer in model group than that of sham operation group, while which was significantly lower in CD147 group than that of model group (P<0.05). The number of times across the platform and the time of staying on platform were significantly lower in model group than those of sham operation group, while which was significantly higher in the CD147 group than that of model group (P<0.05). The expressions of Aβandγ-secretase were increased significantly in model group compared to those of sham operation group, while which were significantly decreased in CD147 group compared with those of model group (P<0.05). Conclusion Exogenous CD147 can significantly improve the learning and memory ability of AD rats, and its specific mechanism may be related to regulating the activity ofγ-secretase and down regulating the expression of Aβ.