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

Effect of galantamine on astrocyte activation and C/EBPβ expression in APP/PS1 transgenic mice

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APP/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5mg/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7d,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/EBPβ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。

Objective To investigate the effect of chronic galantamine treatment on cognitive performance,astrocyte activation and the expression of C/EBPβin the transgenic APP/PS1 mouse model with Alzheimer disease（AD）.Methods Galantamine（5mg/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 7days.Astrocyte activation and C/EBPβexpression levels in hippocampus were observed by immunohistochemistry,immunofluorescence and Western blot methods.ResultsCompared with the normal control group,the model control group and the treatment group exhibited significantly longer escape latencies（P0.05）and significantly decreased platform crossings numbers（P〈0.05）as assessed by Morris water maze test on Days 5and 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/EBPβexpression（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.