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氟西汀调控胎鼠神经干细胞增殖中Notch1通路基因表达的改变
作者:隋毓秀 张志珺 郭怡菁  
单位:南京医科大学附属脑科医院
关键词:神经干细胞 氟西汀 Notch1信号系统 
分类号:
出版年·卷·期(页码):2010·29·第五期(509-514)
摘要:

目的 探讨Notch1信号系统与氟西汀促进神经干细胞(NSCs)增殖的关系。方法 不同浓度的氟西汀干预体外培养的NSCs,通过四甲基偶氮唑盐法(MTT)检测其对细胞活力的影响,获取最适作用浓度。分别予Notch1信号通路抑制剂DAPT和氟西汀干预NSCs后,采用MTT检测NSCs的增殖,real time-PCR法检测Notch1信号各因子的基因表达。结果 (1)氟西汀浓度超过40μmol/L浓度时,可降低NSCs活性,差异有统计学意义(P<0.01或P<0.05);(2) 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0 μmol/L组,差异有统计学意义(P<0.01);(3) 与对照组相比,氟西汀组的细胞活性增高,DAPT组的活性降低,差异均有统计学意义(P<0.001)。与氟西汀干预组相比,氟西汀+DAPT组细胞活性降低,差异有统计学意义(P<0.001);(4) 与对照组相比,DAPT组Hes1mRNA 和Hes5mRNA表达显著降低(P<0.001);与对照组相比,氟西汀组Notch1 mRNA、Hes1 mRNA和Hes5 mRNA表达显著增高(P<0.001 or P<0.01);与氟西汀干预组相比,氟西汀+DAPT组的Notch1 mRNA、Hes1 mRNA和Hes5 mRNA表达均显著降低(P<0.001)。结论(1)氟西汀促进神经干细胞的增殖;(2)氟西汀可以上调Notch1信号系统的表达;(3)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 involves Notch1 signaling in cultured neural stem cells (NSCs). Methods The MTT assay was used to evaluate cell viability. The expression of Notch1 signaling components (including Notch1 mRNA, Hes1 mRNA and Hes5 mRNA) were detected by real time PCR. Results (1) The cell viability was significantly decreased when the concentration of fluoxetine was more than 40μmol/L (P<0.01 or P<0.05). (2) When the cells were treated with the 10μmol/L, 15μmol/L and 20μmol/L fluoxetine for 48h, the cell viabilities in cell-conditioned media increased significantly more than that of the 0μmol/L group (P<0.01). (3) MTT assay showed the presence of fluoxetine strongly enhanced the cell proliferation (P<0.001) compared to control, while DAPT decreased cell proliferation (P<0.001). When adding fluoxetine and DAPT in combination, the cells of proliferation were declined (P<0.001) compared with fluoxetine group. (4) Inactivation of Notch signaling with DAPT lead to a rapid reduction in the expression of Hes1mRNA and Hes5mRNA compared with the control (P<0.001). After the treatment of fluoxetine for 48h, the expression of Notch1mRNA, Hes1mRNA and Hes5mRNA increased significantly compared with the control (P<0.001 or P<0.01). When NSCs were exposed to fluoxetine-conditioned medium with DAPT, real time PCR analysis revealed that the expression of Notch1mRNA, Hes1mRNA and Hes5mRNA were decreased relative to fluoxetine-conditioned medium without DAPT (P <0.001 in all case). Conclusion (1) Fluoxetine enhanced cell proliferation in cultured NSCs. (2) Fluoxetine activated the Notch1 signaling pathway in NSCs. (3) Notch1 signaling might play a major role in the proliferation of NSCs promoted by fluoxetine.

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