依托孕烯对阿尔茨海默病大鼠学习记忆的影响  

Effect of dorsal hippocampal etonogestrel infusions on learning and memory in rats with Alzheimer disease and the mechanism

作　　者：祁旦巳[1] 王孝庆[2] 王中苏[2] 叶莉莎[2] 王斌[2] 曹红[2] 李军[1] 

机构地区：[1]浙江省温州医科大学附属第二医院病理科,温州325027 [2]浙江省温州医科大学附属第二医院麻醉科,温州325027

出　　处：《中华实验外科杂志》2016年第5期1256-1259,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金（81271204）;浙江省自然科学基金（Y2100231）;浙江省医药卫生优秀青年科技人才专项基金（2008QN025）

摘　　要：目的 建立大鼠阿尔茨海默病（AD）模型,观察背侧海马注射依托孕烯对AD大鼠学习记忆能力、海马γ-氨基丁酸（GABA）A受体α1亚基（GABAAα1）及γ-氨基丁酸转运蛋白-1（GAT-1）表达的影响.方法 雄性SD大鼠36只,体重230～270 g,双侧基底核各注射IBO 8 μg建立AD模型,成模后随机分为4组（n=9）：假手术组（Sham组）、溶剂对照组（Con组）、依托孕烯组（ENG组）、GABAA受体拮抗剂组（BIC组）.术后1周行连续6d的Morris水迷宫定位航行实验检测大鼠学习记忆能力,Con、ENG、BIC组在测试第1、2d后2h内背侧海马给予相应药物,BIC组在ENG海马给药前30 min腹腔注射8 mg/kg荷包牡丹碱.免疫组织化学法（n=6）和Western blot法（n=3）检测各组海马CA1/3区GABAAα1及GAT-1的表达.结果 分别与Sham组及Con组比较,ENG组及BIC组大鼠平均逃避潜伏期（AEL）均明显缩短（P＜0.05）,海马CA1/3区GABAAα1阳性细胞数均显著减少[CA1：（5.9±0.7）、（6.6±1.0）个比（3.7±0.8）、（3.1±0.4）个;CA3：（5.9 ±1.3）、（6.2±0.6）个比（3.8±0.6）、（2.8±0.6）个,P＜0.01],CA3区GAT-1阳性细胞均显著减少[（23.7±2.3）、（23.0±1.7）个比（18.3±1.8）、（17.6±2.4）个,P＜0.01],海马GABAAα1（P＜0.05）和GAT-1（1.7±0.5、1.7±0.4比0.9±0.4、0.5±0.2,P＜0.01）蛋白表达水平均明显降低.4组间CA1区GAT-1阳性细胞数差异无统计学意义（P＞0.05）;ENG组和BIC组比较差异无统计学意义（P＞0.05）.结论 依托孕烯可显著改善AD大鼠学习记忆能力,其机制与调节GABA受体水平的表达有关,其中GABAAα1及GAT-1可能参与其中记忆功能的调节作用.Objective To investigate the effects of dorsal hippocampal etonogestrel injection on learning and memory,expression of γ-aminobutyric A receptor alpha 1 subunit （GABAAα1） or γ-aminobutyric transporter-1 （GAT-1） in hippocampal hippocampus CA1 （CA1） and hippocampus CA3 （CA3） areas of rat model of alzheimer disease （AD）.Methods Thirty-six male SD rats weighing 230-250 g were selected in study.All rats were induced by bilateral ibotenic acid （IBO） lesions of the NBM region.After surgery,rats were randomly divided into four groups （n =9 each）：sham-operated group （Sham group）,solvent control group （Con group）,etonogestrel treatment group （ENG group） and antagonist of GABAA group （BIC group）.One week after surgery,average escape latency （AEL） was tested in the Morris water maze with 4 trials per session on 6 successive days.In the first and second day,rats received bilateral dorsal hippocampal injections of vehicle or etonogestrel 2 h after training.However bicuculline was intraperitoneally injected 30 min before bilateral dorsal hippocampal injections of etonogestrel in BIC group.All rats were killed on the last day after test.Immunohistochemistry and Western blotting techniques were used to abserve the expression level of GABAAα1 and GAT-1 in hippocampal CA1 and CA3 area.Results As compared with Sham group and Con group,AEL in ENG group and BIC group was significantly reduced （P 〈 0.05）.The number of GABAAo1 positive cells in hippocampal CA1/3 areas in ENG group was significantly less than in Sham groups [CA1：（5.9 ±0.7）,（6.6 ± 1.0） cells vs.（3.7 ± 0.8）,（3.1±0.4） cells;CA3：（5.9±1.3）,（6.2±0.6） cells vs.（3.8±0.6）,（2.8±0.6） cells,P 〈 0.01].The number of GAT-1 positive cells in hippocampal CA3 in ENG group was significantly reduced [（23.7±2.3）,（23.0±1.7） cells vs.（18.3±1.8）,（17.6±2.4） cells,P〈0.01].The protein levels of GABAAα1 （P 〈 0.05） and GAT-1 （1.7 ± 0.5,1.7 ± 0.4 vs.0.9 ± 0.4,0.5

关 键 词：阿尔茨海默病 依托孕烯 学习 记忆 Γ-氨基丁酸 

分 类 号：R749.16[医药卫生—神经病学与精神病学]