喹硫平对阿尔茨海默小鼠淀粉样β蛋白42表达的影响及机制研究

目的探索喹硫平对阿尔茨海默小鼠淀粉样β蛋白42(Aβ42)的表达的影响及其机制。方法C57BL/6小鼠20只作为对照组,APP/PS1小鼠40只分为APP/PS1组、APP/PS1+喹硫平组,各20只。APP/PS1+喹硫平组小鼠通过腹腔给予喹硫平溶液2.5 mg/(kg·d),连续给药2个月,对照组和APP/PS1组小鼠每天腹腔给予等量双蒸水。通过新事物识别实验检测三组小鼠的记忆功能;通过Western blot检测三组小鼠海马脑区Aβ42蛋白、核因子-κB(NF-κB)p65蛋白的表达水平;通过酶联免疫吸附(ELISA)检测海马脑区白细胞介素-1β(IL-1β)和肿瘤坏死因子α(TNF-α)的表达水平,免疫荧光染色计算小胶质细胞数量。结果与对照组比较,APP/PS1小鼠对新事物的探索时间显著降低(P<0.05),小胶质细胞明显激活,小胶质细胞的数量显著增加(P<0.05),IL-10和TNF-α的表达水平均显著增加(P<0.05),Aβ42、NF-κB p65蛋白表达水平显著增加(P<0.05);与APP/PS1组比较,APP/PS1+喹硫平组小鼠的探索时间显著延长(P<0.05),小胶质细胞数量显著减少(P<0.05),IL-10和TNF-α表达水平均显著降低(P<0.05),Aβ42、NF-κB p65蛋白表达水平显著降低(P<0.05)。结论喹硫平能降低Aβ42蛋白的产生,促进AD小鼠的记忆功能恢复,其发生机制可能与小胶质细胞激活和NF-κB信号通路活化相关。

Effects of quetiapine on amyloid beta protein 42 expression in Alzheimer's mice and its mechanism

Objective To explore the expression and mechanism of quetiapine on amyloid beta protein 42 in Alzheimer's mice.Methods 20 C57BL/6 mice were used as the control group.40 APP/PS1 mice were divided into APP/PS1 group and APP/PS1+quetiapine group.Mice in APP/PS1+quetiapine group were given quetiapine solution(2.5 mg/kg/day)through abdominal cavity for 2 months,while mice in the control group and APP/PS1 group were given the same amount of double steamed water in abdominal cavity every day.The memory function of three groups of mice was tested by new object recognition experiment.Western blot analysis was performed to detect the expression levels of proteins A beta 42 and NF-κB p65 in the hippocampus of the three groups of mice.The expression levels of IL-1beta and TNF alpha in the hippocampus were detected by ELISA,and the number of microglia cells was calculated by immunofluorescence staining.Results Compared with the control group,the time to explore new things in APP/PS1 mice was significantly reduced(P<0.05),microglial cells were significantly activated,and the number of microglial cells was significantly increased(P<0.05).The levels of IL-10 and TNF-αexpression were significantly increased(P<0.05),the levels of Aβ42,NF-κB p65 protein expression were significantly increased(P<0.05).Compared with APP/PS1 group,the time to explore new things in APP/PS1+quetiapine group mice was significantly increased(P<0.05),the number of microglia was significantly reduced(P<0.05),the the levels of IL-10 and TNF-αexpression were significantly reduced(P<0.05),and the levels of Aβ42 and NF-κB p65 proteins expression were significantly reduced(P<0.05).Conclusion Quetiapine can reduce the production of A beta 42 protein and promote the restoration of memory function in AD mice,and its pathogenesis is related to the activation of microglia cells and the activation of NF-κB signaling pathway.