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目的:观察亚甲蓝对APP/PS1转基因小鼠学习记忆及胶质纤维酸性蛋白(Glial fibrillary acidic pro-tein,GFAP)在海马结构表达变化的影响。方法:20只3月龄APP/PS1小鼠,随机分2组,每组10只,对照组:自由饮水;治疗组:根据小鼠饮水量将亚甲蓝加入日常饮水中(25 mg/kg/d)连用4个月至7月龄。水迷宫测试观察其行为学的改变,免疫组化、Western Blot和TUNEL染色法观察GFAP在海马结构的表达及神经元的凋亡情况。结果:水迷宫测试结果显示亚甲蓝喂养组APP/PS1转基因小鼠第2～4 d的平均潜伏期显著低于对照组小鼠的潜伏期,说明治疗组与对照组相比在7个月时出现明显差异(P<0.05);免疫组化和Western结果显示治疗组海马结构内的GFAP在APP/PS1转基因小鼠的表达下调(P<0.05)。TUNEL染色法显示治疗组海马CA1、CA3区和齿状回TUNEL阳性细胞数较对照组明显减少(P<0.05)。结论:亚甲蓝能够下调APP/PS1小鼠海马结构内GFAP蛋白的表达,并通过抑制海马结构神经元的凋亡,提高APP/PS1小鼠的认知能力。
Objective: To observe the effects of methylene blue on learning and memory and the expression of glial fibrillary acidic pro-tein (GFAP) in hippocampus of APP / PS1 transgenic mice. Methods: 20 APP-PS1 mice of 3 months old were randomly divided into 2 groups with 10 rats in each group. The control group was given free drinking water. The treatment group was treated with 25 mg / kg of methylene blue / d) for 4 months to 7 months of age. Water maze test was used to observe the behavioral changes. Immunohistochemistry, Western Blot and TUNEL staining were used to observe the changes of GFAP expression in hippocampal formation and neuronal apoptosis. Results: The results of water maze test showed that the average incubation period of APP-PS1 transgenic mice in 2 ~ 4 d of methionine-fed group was significantly lower than that of the control group, indicating that the treatment group appeared at 7 months compared with the control group (P <0.05). The results of immunohistochemistry and Western analysis showed that the expression of GFAP in APP / PS1 transgenic mice was down-regulated in hippocampal formation of treatment group (P <0.05). TUNEL staining showed that the number of TUNEL-positive cells in hippocampal CA1, CA3 area and dentate gyrus in treatment group was significantly lower than that in control group (P <0.05). Conclusion: Methylene blue can down-regulate the expression of GFAP in hippocampus of APP / PS1 mice and increase the cognitive ability of APP / PS1 mice by inhibiting the apoptosis of hippocampal neurons.