西酞普兰、氟西汀对NGF诱导的PC12细胞活性以及TH和pERK1／2表达的影响

目的观察西酞普兰和氟西汀两种药物对PC12细胞活力及酪氨酸羟化酶（TH）和磷酸化细胞外信号调节激酶（pERK1／2）表达的影响。方法以NGF诱导后的PC12细胞作为细胞模型，给予5，10，20，50gm不同剂量西酞普兰和氟西汀，分别进行直接作用和保护作用处理24或48h（直接作用为直接给予不同剂量齐拉西酮，保护作用为直接作用后再进行12h的去血清损伤）。采用细胞计数试剂盒-8（CCK-8）检测细胞活性，免疫组织化学检测TH和pERK1／2的表达水平的变化。结果分别处理24h后，两种药物在剂量为20μm时均可促进PC12细胞的活性（与对照组相比较，P〈0．01），而且相同浓度的两种药物对细胞活力的作用没有统计学差异（P〉0．05）。药物作用48h后，西酞普兰10μm组对PC12细胞活力具有保护作用（与对照组相比较，P〈0．05），西酞普兰20μm组对PC12细胞活力的促进作用和保护作用均高于氟西汀20μm组（P〈0．05），而且氟西汀在作用48h后对细胞表现出毒性作用（与对照组相比较P〈0．01）；PC12细胞TH和pERK1／2的表达随着药物浓度5μm到20μm逐渐升高，但是在药物浓度为50μm时表达下降，其中氟西汀50μm时TH和pERK1／2的表达低于对照组（P〈0．01）；西酞普兰20μm组TH和pERK1／2的表达均高于氟西汀20μm组（P〈0．05）。结论中剂量的西酞普兰和氟西汀两种药物对PC12细胞活力都有促进作用，都可促进TH的表达，而且这种作用可能是通过ERK途径产生的；西酞普兰对PC12细胞的保护作用优于氟西汀，而且高剂量的氟西汀表现出细胞毒性作用。

Effect of citalopram and fluoxetine on the NGF-induced cell viability and the expression of TH and pERK1/2 in PC12 cells

Objective To investigate the effect of citalopram and fluoxetine on NGF--induced viability of rat pheochromocytoma （PC12） ceils and the expression of tyrosine hydroxylase （TH）and phosphorylated extracellular signal--regulated kinase （pERK1/2） in PC12 cells. Methods Cultured PC12 cells were pretreated or directly treated with different concentrations of citalopram and fluoxetine for 24 or 48 hours and the pretreated groups were then subjected to serum withdrawal condition for 12 h. Cell viability, the expression of Tyrosine hydroxylase （TH） and pERK1/2 was determined using the cell counting Kit-8 （CCK-8） and immunohistochemistry respectively. Results The viability of NGF--induced PC12 was improved 24 h after administration with both drugs at 20 （P 〈 0.01）. At 48 h post-- drug administration, the cell activity of PC12 in 20 μm citalopram was significantly higher as compared with fluoxetine group （P 〈 0.05）. High dose （50μm） of fluoxetine demonstrated high toxicity to PC12 ceils, which was not seen with citalopram. The expression of both TH and pERK1/2 was increased by treatment of citalopram 10 μm and 20 μm and fluoxetine 20 μm group comparing to control group at 48 h. The expression of TH and pERK1/2 expression was significantly higher in citalopram 20μm than that in the same concentration of fluoxetine （P 〈 0.05）. The expression of TH and pERK1/2 in fluoxetine 50 μm, however, decreases significantly comparing to control group （P 〈 0. 01）. Conclusions These data suggest that citalopram and fluoxetine in medium concentration could protect PC12 cells and this effect might be mediated through TH and pERK1/2 signal pathways. Citalopram has larger safe and effective dose window than fluoxetine which might be toxic at higher concentration.