摘要
目的研究舍曲林对对NGF诱导的PCI2细胞细胞活力以及酪氨酸羟化酶（TH）和磷酸化细胞外信号调节激酶1／2（pERKI／2）表达的影响。方法以NGF诱导后的PCI2细胞为细胞模型，给予5μM、10μM、20μM、50μM不同剂量舍曲林，分别进行直接作用和保护作用处理后，采用细胞计数试剂盒．8（CCK-8）检测细胞活性，免疫组织化学观察细胞形态学改变以及蛋白质斑迹法（westernblot）检测PCI2细胞酪氨酸羟化酶（TH）和磷酸化细胞外信号调节激酶（pERK1／2）的表达水平的变化。结果中等剂量的舍曲林促进PC12细胞的活性，直接作用24h后20μM（1．32±0．11）、10μM（1．17±0．05），保护作用24h后20μM（1．15±0．11）显著高于对照组，高剂量50μM的舍曲林PCI2细胞有很强的毒性作用。20μM舍曲林直接作用后PCI2细胞TH表达增加，TH与13-aetin表达阳性面积的比值24h作用组（1．27±0．05）以及48h作用组（1．23±0．08）与对照组（作用24h和48h分别为0．99±0．04，0．92±0．07）相比差异有统计学意义沪〈0．01，P〈0．05），20μM舍曲林直接作用后PCI2细胞pERK1／2表达也增加，pERK1／2与β-actin表达阳性面积的比值24h作用组（1．41±0．05）以及48h作用组（1．40±0．06）与对照组（作用24h和48h分别为0．86±0．04，0．78±0．06）相比差异有统计学意义（P〈0．01，P〈0．05），免疫组织化学结果与上述-致。结论舍曲林能提高PCI2细胞的活性，对神经元提供保护可能是舍曲林抗抑郁作用机制之-，而这种作用可能是通过上调TH以及pERK1／2的表达实现的。
Objective To investigate the effect of sertraline on the viability and the expression of tyrosine hydroxylase （TH） and phosphorylated ERK1/2 in NGF-induced rat pheochromocytoma （PC12） ceils. Methods NGF-induced PC12 cells were pretreated or directly treated with different concentrations of sertraline for 24 or 48 hours and the pretreated groups were then subjected to serum withdrawal condition. Then cell viability was determined by the cell counting Kit-8 （CCK-8）. The expression of Tyrosine hydroxylase （TH） and pERK1/2 in NGF-induced PC12 cells was determined by immunohistochemistry and western blot respectively. Results The viability of NGF-indnced PC12 was improved after administration with sertraline. After 24h sertraline administration,the cells activity of PC12 cells at 20μM （ 1.32 ±0.11 ） , 10μM （ 1. 17 ± 0. 05） of direct effect, and 20μM （1.15 ±0. 11 ） of protect effect increased dramatically as compared with control group. But high dose （50pμM） sertraline express high toxic effect to PCI2 cells. The expression of TH was increased by sertraline 20μM at both 24h（ ratio of TH/β-actin = 1.27 ±0.05 ） and 48h （ratio of TH/β-actin = 1.23 ± 0. 08 ） compare with control group, and the expression of pERK1/2 also increased dramatically by sertraline 20 μM at both 24h （ratio of （ pERK1/2 ）/β-actin = 1.41 ± 0.05 ） and 48h （ ratio of （ pERK1/2 ）/β-actin =1. 40 ± 0. 06） compare with control group（P 〈0.01, P 〈 0. 05 ）. Immunohistochemistry showed similar results. Conclusion These data suggest that the neuroprotective effect of sertraline may play an important role in depression therapy, and this effect might be mediated by TH and pERK1/2 up-regulation.
出处
《中华行为医学与脑科学杂志》
CAS
CSCD
北大核心
2010年第12期1090-1092,共3页
Chinese Journal of Behavioral Medicine and Brain Science
基金
基金项目：国家自然科学基金（30870886）
