氟西汀对神经干细胞增殖和Notch1信号通路相关蛋白表达的影响  

Fluoxetine increases cell proliferation and activation of Notch1 signaling in cultured rat neural stem cells

作　　者：隋毓秀[1] 张志珺[1] 郭怡菁[1] 孙奕[1] 

机构地区：[1]东南大学附属中大医院神经内科,江苏南京210009

出　　处：《南京医科大学学报（自然科学版）》2010年第9期1227-1230,1323,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金资助(30600206,30770779)

摘　　要：目的:探讨Notch1信号系统在氟西汀促进神经干细胞(neural stem cells,NSCs)增殖中的作用。方法:不同浓度的氟西汀干预神经干细胞,获取最适作用浓度。分别予γ泌肽酶抑制剂(DAPT)和氟西汀干预神经干细胞后,采用MTT检测神经干细胞的增殖,Western Blot法检测Notch1信号各因子的蛋白表达。结果:①不同浓度的氟西汀干预细胞48h后,10μmol/L、15μmol/L和20μmol/L组NSCs的活性高于0μmol/L组;②与对照组相比,氟西汀组的细胞活性增高,DAPT组的活性降低;与氟西汀干预组相比,氟西汀+DAPT组细胞活性降低;③与对照组相比,DAPT组Hes1和Hes5蛋白表达水平显著降低;与对照组相比,氟西汀组NICD、Hes1和Hes5蛋白表达水平显著增高;与氟西汀干预组相比,氟西汀+DAPT组的NICD因子、Hes1因子和Hes5因子蛋白表达水平均显著降低。结论:氟西汀促进神经干细胞的增殖;氟西汀可以上调Notch1信号系统的表达;氟西汀可能通过调控Notch1信号的传导促进NSCs的增殖。Objective：To investigate whether the effect of fluoxetine on cell proliferation involving Notch1 signaling in cultured neural stem cells（NSCs）.Methods：The MTT assay was used to evaluate cell viability.The protein level of Notch1 signaling components（including NICD,Hes1 and Hes5） were detected by Western blot.Results：①When the cells were treated with the 10 μmol /L,15 μmol/L and 20 μmol/L fluoxetine for 48 h,the cell viabilities increased significantly more than those without fluoxetina treated.② MTT assay showed the presence of fluoxetine strongly enhanced the cell proliferation compared to the control,while DAPT decreased cell proliferation.When fluoxetine and DAPT in combination were added,the cells of proliferation were declined compared with single fluoxetine treated group.③ Inactivation of Notch signaling with DAPT lead to a rapid reduction in the protein expression level of Hes1and Hes5 compared with the control.After the treatment of fluoxetine for 48 h,the protein expressions of NICD,Hes1 and Hes5 increased significantly compared with the control.When NSCs were exposed to fluoxetine-conditioned medium with DAPT,western blot analysis revealed that the levels of NICD,Hes1 and Hes5 were decreased relative to fluoxetine-conditioned medium without DAPT.Conclusion：①Fluoxetine enhanced cell proliferation in cultured NSCs.②Fluoxetine activated the Notch1 signaling pathway in NSCs.③ Notch1 signaling play a major role in the proliferation of NSCs promoted by fluoxetine.

关 键 词：神经干细胞 氟西汀 Notch1信号系统 

分 类 号：R392.12[医药卫生—免疫学]