氟西汀对阿尔茨海默病神经细胞模型保护作用分子机制的研究分析  

Study and Analysis of the Molecular Mechanism of Neuroprotective Effect of Fluoxetine on the Nerve Cell Model of Alzheimer's Disease

作　　者：李曌[1] 况超[1] 李刚[1] 叶柳[1] 熊伟[1] 陈雄斌[1] 李晓朋[1] 戴颂扬 朱殷青 张蕾[1] 孟赞[1] 唐勇[1] 刘永刚[1] 

机构地区：[1]重庆医科大学基础医学院组织细胞工程与干细胞研究室病理学教研室,重庆400016

出　　处：《基因组学与应用生物学》2016年第1期1-5,共5页Genomics and Applied Biology

基　　金：国家自然科学基金(81171238;31271288)资助

摘　　要：本研究初步探讨氟西汀(fluoxetine)对阿尔茨海默病(Alzheimer's disease,AD)神经细胞模型小鼠神经纤维瘤细胞,野生型N2A/WT细胞和β-淀粉样蛋白(amyloidβ-protein,Aβ)过表达型N2A/APP695swe细胞的保护作用及可能机制。CCK-8法进行氟西汀对APP695细胞抑制率的测定,以半数抑制率(IC50)的氟西汀浓度作为后续实验的药物浓度。后分为WT组、APP695+氟西汀组、APP695组,三组细胞分别培养48 h后,进行细胞原位凋亡染色。最后以Western测定Aβ和BDNF的表达量。实验结果测得半数抑制率(IC50)的氟西汀浓度10-7mol/L。细胞凋亡染色结果显示APP695组凋亡的细胞明显多于其他两组(p<0.01),与APP695+氟西汀组相比凋亡细胞增加(p<0.05),而WT组与APP695+氟西汀组凋亡细胞无显著性差异(p>0.05)。Western结果显示APP695组Aβ表达多于其他两组(p<0.05)而BDNF表达明显少于其他两组(p<0.01),与APP695+氟西汀组相比Aβ表达增加(p<0.05)但BDNF表达减少(p<0.05),而WT组与氟西汀组相比Aβ和BDNF的表达量均无显著性差异(p>0.05)。本研究结果提示氟西汀可以通过抑制APP695过表达Aβ,从而减少有毒Aβ对BDNF的影响,增加BDNF的表达量,对神经细胞起保护作用,为氟西汀治疗AD提供新的思路。The possible mechanism of neuroprotective effect of fluoxetine on the nerve cell model including N2A/WT cells and N2A/APP695swe cells of Alzheimer＇s disease was preliminarily discussed in this study. Firstly, the inhibition rate of APP695 cells was measured by CCK-8 experiment, and half inhibition rate （IC50） of fluox- etine concentration was selected as the drug concentration on the subsequent experiments. Secondly, WT group, APP695 ＋ fluoxetine group, and APP695 group were divided, of which the cells were in Apoptosis staining experiments after being cultured for 48 hours. Finally, the expression of Aβ and BDNF was determined by Wes- tern. The result of CCK-8 experiment showed half inhibition rate （IC50） of fluoxetine concentration was 10^-7 mol/L. The result of situ apoptosis staining showed that apoptotic cells of APP695 group were significantly more than the other two groups （p 〈0.01）, apoptotic cells increased （p 〈0.05） when compared with the APP695＋ fluoxetine group, whereas, there was no significant difference between WT group and APP695＋ fluoxetine group （p 〉0.05）. Western result showed that Aβ expression in APP695 group was more （p〈0.05） while BDNF expression was significantlyless （p〈0.01） when compared with the other two groups, and Aβ expression increased （p〈0.05） while of BDNR expression decreased （p 〈0.05） when compared with APP695 ＋fluoxetine group, while there was no significant difference of Aβ and BDNF expression （p〉0.05） between WT group and fluoxetine group. The results suggested that fluoxetine may inhibit APP695 overexpressing Aβ, thereby it might reduce the impact of toxic A[β to BDNF, and then increase the expression of BDNF to save nerve cell, which provided new ideas for treatment of Fluoxetine on Alzheimer＇s disease.

关 键 词：阿尔茨海默病 氟西汀 Β-淀粉样蛋白 BDNF 

分 类 号：R749.16[医药卫生—神经病学与精神病学]