Notch1信号系统在氟西汀上调大鼠海马神经再生中的作用

目的 了解慢性氟西汀干预正常大鼠所导致的海马神经再生上调与Notch1信号系统功能改变的关系.方法 应用大鼠腹腔注射氟西汀建立在体模型,分为对照组、14 d干预组、28 d干预组(n=12),采用免疫组化、real time PCR和Western blot,测定大鼠海马神经干细胞的增殖、存活和分化以及Notch1信号通路各个因子(NICD、Hes1、Hes5、Jag1)的基因及蛋白表达水平的改变.结果 ①与对照组(2919.50±188.80)比较,14 d氟西汀干预组(3706.50±228.04)、28 d氟西汀干预组(4334.33±217.48)海马齿状回神经干细胞增殖明显增加(P<0.001);与对照组(2404.50±148.77)相比,Flu干预28 d组(3273.16±156.68)海马齿状回神经干细胞存活明显增加(P<0.001);与对照组比较,氟西汀干预组NeuN/BrdU、GFAP/BrdU比例无明显差异(P＞0.05).②与对照组[NICDmRNA (0.30±0.03),Hes1mRNA (0.53±0.03),Hes5mRNA (0.21±0.02),Jag1mRNA(1.04±0.07)]比较,氟西汀(Flu)干预14d组[NICDmRNA (0.45±0.05),Hes1mRNA (0.65±0.06),Hes5mRNA (0.31±0.06),Jag1mRNA(2.46±0.39)]和Flu干预28 d组[NICDmRNA (0.42±0.03),Hes1mRNA (0.85±0.06),Hes5mRNA (0.39±0.02),Jag1mRNA(3.21±0.34)]Notch1信号通路各因子基因水平均明显升高(P<0.01或P<0.001).③与对照组[NICD(2.36±0.17),Hes1(1.09±0.25),Jag1(2.33±0.31)]比较,Flu干预14 d组[NICD(3.20±0.25),Jag1(2.86±0.25)]和Flu干预28 d组[NICD(3.40±0.19),Hes1(1.43±0.13),Jag1(3.35±0.14)]NICD、Hes1、Jag1蛋白水平明显升高,差异有统计学意义(P<0.01或P<0.001).与对照组Hes5比较,Flu干预14 d组Hes5和Flu干预28 d Hes5蛋白水平无改变,差异无统计学意义(P＞0.05).结论 氟西汀促进大鼠海马齿状回神经干细胞的增殖和存活,但对分化无影响;同时,海马Notch信号功能激活,提示Notch1信号系统可能参与氟西汀介导的大鼠海马神经再生上调.

The role of Notch1 signaling in neurogenesis in the rat hippocampus after chronic fluoxetine administration

Objective To investigate whether the effect of fluoxetine on hippocampal neurogenesis involves Notch1 signaling.Methods The Notch1 signaling pathway was investigated using real time PCR and Western blot at 14 d and 28 d following fluoxetine administration.Neurogenesis was determined by assessing cell proliferation,survival and differentiation.Results mRNA and protein expression levels of Notch1 signaling components(including Jag1,NICD and Hes1) in the hippocampus increased after fluoxetine administration,ac...