不同浓度Aβ25-35蛋白模拟阿尔茨海默病模型学习记忆的差异

摘要

目的 不同浓度的淀粉样蛋白Aβ25-35侧脑室注射后,观察大鼠Morris水迷宫学习记忆能力的变化,探讨制备AD模型大鼠时Aβ25-35注射的最佳浓度.方法 雄性SD大鼠随机分为假手术组和模型组,模型组Aβ25-35注射浓度分别为2、4和8 μg/μL.参照《大鼠脑立体定位图谱》,选取右侧侧脑室注射聚集态的Aβ25-35,制备AD大鼠模型.造模成功后7 d采用Morris水迷宫测试各组大鼠学习记忆能力的变化.结果 平均游泳速度比较,各组大鼠间差异无显著性(P > 0.05).逃避潜伏期结果显示,与假手术组比较,模型组大鼠逃避潜伏期时间明显增加,差异有显著性(P < 0.05);模型组中,与注射2 μg/μL的大鼠比较,注射4 μg/μL与8 μg/μL后大鼠逃避潜伏期时间明显增加,差异有显著性(P < 0.05);4 μg/μL与8 μg/μL组间比较,差异无显著性(P > 0.05).目标象限的活动时间与路程显示,与假手术组比较,模型组注射不同剂量Aβ25-35的大鼠目标象限活动时间和路程均显著减少,差异有显著性(P < 0.05),但模型组不同浓度间比较差异无显著性(P > 0.05).空间探索结果显示,与假手术组比较,模型组注射不同剂量Aβ25-35的大鼠穿越平台次数均显著减少,差异有显著性(P < 0.05);模型组中,与注射2 μg/μL的大鼠比较,注射4 μg/μL和8 μg/μL后大鼠穿台次数明显减少,差异有显著性(P < 0.05).4 μg/μL与8 μg/μL组间比较,差异无显著性(P > 0.05).结论 单侧侧脑室注射Aβ25-35蛋白制备大鼠AD模型时,注射Aβ25-35的推荐浓度为4μg/μL.%Objective To observe the learning and memory ability of rats after injection of Aβ25-35 protein in different concentrations into the lateral ventricle assessed by Morris water maze test, and to explore the optimal concentration of Aβ25-35 in the preparation of AD model rats.Methods Male SD rats were randomly divided into sham operated group and model group.The rats of model group received Aβ25-35 injection in concentrations of 2 μg/μL, 4 μg/μL and 8 μg/μL, respectively.According to the Rat Brain Stereotaxic Atlas, 5 μL of aggregation of Aβ25-35 was injected into the right lateral ventricle to establish the AD rat model.7 days after successful modeling, Morris water maze was used to test thechanges of learning and memory ability of the rats.Results There was no significant difference in the average swimming speed between the two groups (P > 0.05).The escape latency time of rats in the model group was significantly increasedcompared with the sham group (P < 0.05).In the model group, the escape latency time of rats treated with 4 μg/μL and 8 μg/μL Aβ25-35 was significantly increased compared with the rats injected with 2 μg/μL (P < 0.05), while there was no significant difference between rats treated with 4 μg/μL and 8 μg/μL Aβ25-35 (P > 0.05).The activity time and distance of target quadrant of the rats injected with different concentration of Aβ25-35in the model group were significantly reduced compared with the sham group (P < 0.05), but no significant difference amongthe rats treated with different Aβ25-35 concentrations (P > 0.05).Compared with the sham-operated group, the number of platform-crossing of rats injected with different doses of Aβ25-35in the model group were significantly reduced (P < 0.05).In the model group, the rats treated with 4 μg/μL and 8 μg/μL was significantly reduced compared with the group with 2 μg/μL injection (P < 0.05).There was no significant difference between the rats injected with 4 μg/μL and 8 μg/μL (P > 0.05).Conclusions The recommended dose and concentration of Aβ25-35 to be injected into the unilateral ventricle to establisha rat model of Alzheimer's disease is 4 μg/μL in a volume of 5 μL.