2-BFI改善阿尔茨海默病模型大鼠认知功能的观察研究  

Improvement Effect of 2-BFI on the Cognitive Function in a Rat’s Model of Alzheimer’s Disease

作　　者：杨婷[1] 徐莎莎 陈轲扬[2] 李岩[2] 韩钊[2] 曹云刚[2] Yang Ting;Xu Shasha;Chen Keyang;Li Yan;Han Zhao;Cao Yungang(Department of Emergency,the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Zhejiang Wenzhou 325000,China;Department of Neurology,the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Zhejiang Wenzhou 325000,China)

机构地区：[1]温州医科大学附属第二医院急诊科,浙江温州325000 [2]温州医科大学附属第二医院神经内科,浙江温州325000

出　　处：《中国药师》2021年第5期797-800,共4页China Pharmacist

基　　金：国家自然科学基金项目(编号:81771267);温州市基础性科研项目(编号:Y20190403)。

摘　　要：目的:观察咪唑啉化合物2-(2-苯并呋喃基)-2-咪唑啉(2-BFI)对阿尔茨海默病(AD)模型大鼠认知功能及海马胆碱乙酰转移酶(Ch AT)、淀粉样前体蛋白(APP)表达水平的的影响。方法:32只SD大鼠按随机数字表法分为4组:假手术组、AD模型组、2-BFI低(1.5 mg·kg^(-1))、高剂量组(3 mg·kg^(-1)),每组8只。采用立体定向海马注射β-淀粉样蛋白1-40(Aβ1-40)制作AD模型,2-BFI组腹腔注射相应剂量药物,假手术组和AD模型组给与等量盐水,1次/d,连续给药21 d。采用水迷宫实验分别在第7,14,21天检测各组AD大鼠的行为学,第21天时检测各组大鼠海马ChAT、APP蛋白表达水平。结果:与假手术组比较,AD模型组大鼠在各个时间点的逃避潜伏期延长,跨越平台次数减少(P<0.01);Ch AT蛋白表达明显降低,APP蛋白表达明显升高(P<0.01)。与AD模型组比较,2-BFI低、高剂量组大鼠的逃避潜伏期缩短,跨越平台次数增加,除了低剂量组第7天的逃避潜伏期外,两个剂量组的其余时间点各指标差异均有统计学意义(P<0.05或P<0.01);两个剂量组的Ch AT蛋白表达均明显升高,APP蛋白表达均降低(P<0.01)。假手术组海马神经元规则,细胞形态结构正常;AD模型组神经元细胞减少,大量水肿,排列紊乱,细胞形态改变,出现大面积细胞坏死,大量空泡;2-BFI低、高剂量组大鼠海马组织病理变化均有明显改善。结论:2-BFI能改善AD大鼠的学习记忆能力,能减少Aβ1-40诱导的神经元变性、Aβ的沉积,增加海马区CHAT表达,减少APP表达。Objective:To evaluate the effect of 2-(2-benzofu-ranyl)-2-imidazoline(2-BFI)on the cognitive function of Alzheimer’s disease rat’s model and the expressions of CHAT and APP in hippocampus.Methods:Totally 32 SD rats were divided into 4 groups according to the random number table method:sham operation group,AD model group,2-BFI low(1.5 mg·kg^(-1))and high dose groups(3 mg·kg^(-1))with 8 ones in each group.AD model was made by stereotactic hippocampal injection ofβ-amyloid 1-40(Aβ1-40).The two 2-BFI groups were intraperitoneally injected with the corresponding dose of drug,and the sham operation group and the AD model group were given the same amount of saline,once a day,for 21 consecutive days.The water maze experiment was used to detect the behavior of AD rats in each group on the 7 th,14 th and 21 st days.On the 21 st day,the protein expression levels of Ch AT and APP in hippocampus of each group were detected.Results:Compared with those in the sham operation group,the rats in the AD model group had longer escape latency at various time points,and the number of crossing platforms decreased(P<0.01);Ch AT protein expression was significantly reduced,and APP protein expression was significantly increased(P<0.01).Compared with that in the AD model group,the escape latency of rats in 2-BFI low and high dose groups was shortened and the number of crossing platforms increased;except the escape latency on the 7 th day of the low dose group,the differences in the other indicators at various time points between the two dose groups were all statistically significant(P<0.05 or P<0.01);Ch AT protein expression was significantly increased in the two dose groups,and APP protein expression was decreased(P<0.01).The hippocampal neurons in the sham operation group were regular,and the cell morphology and structure were normal;the AD model group had reduced neuronal cells,large area of edema,disordered arrangement,changes in the cell morphology,large area of cell necrosis,and a large number of vacuoles;the above pathologica

关 键 词：阿尔茨海默病 咪唑啉化合物2-(2-苯并呋喃基)-2-咪唑啉 MORRIS水迷宫 胆碱乙酰转移酶 Β-淀粉样前体蛋白 

分 类 号：R965.1[医药卫生—药理学]