加兰他敏对APP／PS1转基因小鼠海马区星形胶质细活化及C／EBPβ表达的影响

摘要

Objective To investigate the effect of chronic galantamine treatment on cognitive performance , astrocyte activation and the expression of C/EBPβ in the transgenic APP/PS1 mouse model with Alzheimer disease (AD) .Methods Galantamine (5 mg/kg ,i.p.) or 0.9% saline were administrated twice daily for eight weeks in 10‐month‐old male APP/PS1 mice as the treatment group and the model control group.In addition ,a separate group of 10‐month old male C57BL/6 wild type mice was included as a reference normal control group. Morris water maze was applied to evaluate the learning and memory abilities for 7 days. Astrocyte activation and C/EBPβ expression levels in hippocampus were observed by immunohistochemistry , immunofluorescence and Western blot methods. Results Compared with the normal control group , the model control group and the treatment group exhibited significantly longer escape latencies (P<0.05) and significantly decreased platform crossings numbers (P<0.05) as assessed by Morris water maze test on Days 5 and 6.Compared with the model control group , the treatment group exhibited significantly decreased escape latencies ( P < 0.05 ) and significantly increased numbers of platform crossings ( P < 0.05 ) . Galantamine inhibited astrocyte activation and glial fibrillary acidic protein (GFAP) expression [(5.003 ± 0.823)% ] as assessed by immunohistochemistry as well as decreased C/EBPβ expression (87.711 ± 14.622) as determined by immunofluorescence and western‐blot within the hippocampus of transgenic APP/PS1 mice. There was significant difference between the treatment group and the model control group [(7.116 ± 1.040)% ,119.920 ± 16.901] (P<0.05 , respectively) . Conclusions Galantamine improves the learning and memory abilities of APP /PS1 transgenic mice , the mechanism of which may involve inhibition of the activation of astrocytes and the expression of C/EBPβ.%目的：研究加兰他敏对APP／PS1转基因小鼠海马区星形胶质细胞活化、C／EBPβ表达及行为学的影响。方法选取10月龄雄性A PP／PS1转基因小鼠20只，随机分为模型对照组（10只）和治疗组（10只），同月龄、同背景的C57BL／6野生型雄性小鼠10只作为正常对照组。治疗组皮下注射加兰他敏溶液5 mg／kg ，2次／d ，连续治疗8周，正常对照组和模型对照组给予皮下注射等量生理盐水。应用Morris水迷宫实验于干预治疗8周后开始测定各组小鼠空间学习记忆能力，连续7 d ，采用免疫组织化学、免疫荧光及Western‐blot方法观察各组小鼠海马区星形胶质细胞活化及C／EB Pβ表达水平。结果与正常对照组相比，模型对照组和治疗组小鼠Morris检测第5、6天平均逃避潜伏期延长，穿越平台次数减少（P＜0.05，P ＜0.05），而治疗组其逃避潜伏期较模型对照组缩短（P ＜0.05），穿越平台次数增多（P＜0.05）；同时治疗组小鼠星形胶质细胞活化被明显抑制，胶质纤维酸性蛋白（GFAP）的阳性表达面积〔（5.003±0.823）％〕及C／EBPβ的表达量（87.711±14.622）较模型对照组〔（7.116±1.040）％，119.920±16.901〕明显减少（P＜0.05，P＜0.05）。结论加兰他敏改善APP／PS1转基因AD小鼠的学习记忆能力可能与其抑制星形胶质细胞的活化及C／EBPβ的表达有关。