参芪益智颗粒对5XFAD转基因小鼠学习记忆能力和脑内β淀粉样蛋白_(1-42)含量的影响

Effects of Shenqi Yizhi Granules on Ability of Learning and Memory and Content of Aβ_(1-42) of Cerebral Tissue in 5XFAD Mice with Alzheimer's Disease

目的观察参芪益智颗粒对阿尔茨海默病5XFAD转基因小鼠行为学和脑组织β淀粉样蛋白1-42(Aβ1-42)含量的影响,探讨其改善5XFAD小鼠学习记忆能力的作用机制。方法将4月龄C57BL?6野生型小鼠随机分为生理盐水对照组和中药对照组,同时将同月龄5XFAD小鼠随机分为模型组、参芪益智颗粒组和石杉碱甲组,每组15只,各给药组给予相应药物灌胃,连续60 d。给药结束后,采用筑巢实验、避暗实验和Morris水迷宫实验评价各组小鼠学习和记忆能力;免疫组化和免疫荧光方法观察各组小鼠皮层和海马组织老年斑块、Aβ1-42、小胶质细胞激活的标记物小胶质细胞/巨噬细胞特异性蛋白1及星形胶质细胞激活标记物胶质纤维酸性蛋白含量的变化。结果与生理盐水对照组比较,模型组小鼠筑巢实验得分明显降低,避暗实验步入潜入期明显缩短,水迷宫实验逃避潜伏期明显延长,脑内老年斑块明显增多,Aβ1-42含量明显升高,胶质细胞激活明显增强。参芪益智颗粒组小鼠上述指标均恢复或接近至野生型小鼠水平,与模型组小鼠比较差异有统计学意义(P<0.05,P<0.01)。结论参芪益智颗粒改善5XFAD小鼠学习和记忆能力的机制与减少脑内老年斑数量、抑制胶质细胞过度激活、减少脑内Aβ1-42的含量有关。

Objective To study the effects ofShenqi YizhiGranules (SQYZ) on learning and memory and content of Aβ1-42 of cerebral tissue in 5XFAD mice with Alzheimer’s disease; To discuss its mechanism on improving learning and memory ability of 5XFAD mice.Methods Four-month-old C57BL?6 wild type mice were randomly divided into NS control group and SQYZ control group, and the 5XFAD mice were randomly divided into model group, SQYZ group and huperzine-A (HupA) group, 15 mice in each group. Each group were given same volume for gavage for 60 d. After treatment, the learning and memory ability were evaluated by nesting test, passive avoidance and Morris water maze test. The senile plaques and content of Aβ1-42, ionized calcium binding adapter molecule 1 and glial fibrillary acidic protein in cerebral cortex and hippocampus were detected by immunohistochemical staining and immunofluorescence, respectively.Results Compared with NS control group, the score of nesting test in model group significantly decreased; the step-through latency in passive avoidance was shortened and the escape latentcy in Morris water maze test was prolonged; the quantity of senile plaques and content of Aβ1-42 increased in cerebral cortex and hippocampus; the activation of glial cells significantly increased. In the SQYZ group, the above-mentioned indexes reached or approached the level of wild type control mice. The difference between SQYZ group and model group was statistically significant (P<0.05,P<0.01).Conclusion SQYZ improved learning and memory ability in 5XFAD mice, which may be related to reduction of senile plaques, inhibition of over activation in glial cells and reduction of content of Aβ1-42 in cerebral cortex and hippocampus.