氟西汀对阿尔茨海默病模型小鼠的神经元保护作用

中国临床药理学与治疗学 ›› 2015, Vol. 20 ›› Issue (5): 514-519.

氟西汀对阿尔茨海默病模型小鼠的神经元保护作用

李刚^1,2, 况超^1,2, 孟赞^1,2, 周良^1,2, 马晶^1,2, 罗艳敏^1,2, 李曌^1,2, 刘品月^1,2, 何洁³, 唐勇^1,2, 刘永刚^1,2

¹重庆医科大学人体解剖与组织胚胎教研室, ²干细胞与组织工程教研室, ³重庆医科大学附属第一医院神经内科,重庆市 400016

收稿日期:2015-01-30 修回日期:2015-03-07 发布日期:2015-06-11
作者简介:李刚,男,在读硕士,主要从事老年神经退行性改变及阿尔茨海默病研究。Tel: 15023101890 E-mail: 895515260@qq.com
基金资助:
国家自然科学基金(81171238,31271288);重庆市首批“百名学术学科领军人才”培养计划[2012]

Neuroprotective effect of fluoxetine on the APP/PS1 transgenic mouse model of Alzheimer's disease

LI Gang^1,2, KUANG Chao^1,2, MENG Zan^1,2, ZHOU Liang^1,2, MA Jing^1,2, LUO Yan-min^1,2, LI Zao^1,2, LIU Pin-yue^1,2, HE Jie³, TANG Yong^1,2, LIU Yong-gang^1,2

¹ Department of Histology and Embryology, ² Laboratory of Stem Cells and Tissue Engineering, ³ Department of Neurology ,First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

Received:2015-01-30 Revised:2015-03-07 Published:2015-06-11

摘要/Abstract

摘要： 目的: 研究氟西汀对老年APP/PS1双重转基因阿尔茨海默病模型小鼠学习记忆能力的影响及对神经元的保护作用。方法: 实验分为动物实验和细胞实验。动物实验中取APP/PS1双重转基因小鼠随机分为氟西汀组(n=8)和生理盐水组(n=8),另取C57同窝生同月龄正常小鼠10只为对照组。氟西汀组小鼠给予氟西汀(10 mg/kg)腹腔注射,生理盐水组及对照组注射等量生理盐水1次/d,持续8周。Morris水迷宫实验进行行为学检测。Tunel 染色检测海马区神经元凋亡。细胞实验中将人神经母细胞瘤细胞 (SH-SY5Y)培养 48 h 后分为正常组、Aβ组、氟西汀组和氟西汀+Aβ组,后3组分别在含 10 μmol/L β-淀粉样蛋白、100 nmol/L 氟西汀和 100 nmol/L 氟西汀+10 μmol/L β-淀粉样蛋白的DMEM中继续培养48 h。行原位细胞凋亡染色检测各组细胞凋亡。结果: 水迷宫定位航行实验中,氟西汀组小鼠较生理盐水组相比平均潜伏期明显缩短(P<0.01);空间探索实验中跨越平台次数增加(P<0.01);海马区凋亡神经元数量减少(P<0.01)。细胞实验中,氟西汀组和氟西汀+Aβ组与Aβ组相比,凋亡细胞数量明显减少(P<0.01)。结论: 氟西汀对神经元细胞有保护作用,能减少神经元的凋亡,长期服用氟西汀能显著改善APP/PS1阿尔茨海默病模型小鼠学习记忆力能力。

关键词: 阿尔茨海默病, 氟西汀, 凋亡, 神经元, APP/PS1双重转基因小鼠, 认知

Abstract: AIM: To study the neuroprotective effect of fluoxetine and its impact on learning and memory functions in aged APP/PS1 transgenic mouse model of Alzheimer's disease.METHODS: The experiments were performed both in vivo and in vitro. In the in vivo experiment, experimental animals were divided into three groups: APP/PSI AD model group was treated by intragastric injection of Fluoxetine (FLX)(n=8), APP/PS1 AD model saline group (NA)(n=8)and age-matched wild-type litter-mates as the WT group (WT) (n=10). FLX group was given fluoxetine 10 mg/kg by intraperitoneal injection. NA and WT groups were given saline solution. Morris water maze test was used to assess the cognitive behavioristics in each group. Tunel staining was used to assess apoptosis in the hippo campus. In the in vitro experiment, human neuroblastoma cells (SH-SY5Y) cultured for 48 hours were divided into four groups: normal, Aβ, fluoxetine, and fluoxetine + Aβ groups. Except the normal group, cells in the other three groups were respectively cultured with DMEM containing 10 μmol/L β-amyloid, 100 nmol/L fluoxetine and 100 nmol/L fluoxetine + 10 μmol/L β-amyloid, for 48 hours.RESULTS: In Morris water maze tests, the average latency was significantly shorter in the FLX group compared with NS groups (P<0.01) and the average cross platform times in the FLX group was significantly more than the NA group (P<0.01). Tunel experiment showed that FLX group had less apoptotic cells compared with NA group (P<0.01). In the in vitro experiment, the number of apoptotic neurons was significantly lower in the fluoxetine group compared with the Aβ group (P<0.01).CONCLUSION: These findings indicate that fluoxetine has neuroprotective effects on the neurons and long-term administration of fluoxetine can improve the learning and memory ability of the APP/PS1 transgenic mouse model

Key words: Alzheimer's disease, fluoxetine, apoptosis, neuron, APP/PS1 transgenic mouse, cognition

中图分类号:

R965.2

李刚, 况超, 孟赞, 周良, 马晶, 罗艳敏, 李曌, 刘品月, 何洁, 唐勇, 刘永刚. 氟西汀对阿尔茨海默病模型小鼠的神经元保护作用[J]. 中国临床药理学与治疗学, 2015, 20(5): 514-519.

LI Gang, KUANG Chao, MENG Zan, ZHOU Liang, MA Jing, LUO Yan-min, LI Zao, LIU Pin-yue, HE Jie, TANG Yong, LIU Yong-gang. Neuroprotective effect of fluoxetine on the APP/PS1 transgenic mouse model of Alzheimer's disease[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(5): 514-519.

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