【摘要】 目的:探讨抗抑郁剂可能的共同作用机制。方法:以MTT比色法检测细胞活性状态;以Fura 2-AM荧光标记法测定胞内Ca²⁺浓度:以RT-PCR法检测神经生长因子（NGF） mRNA水平。结果:以高浓度皮质酮0.2 mmol/L处理PC12细胞48h以模拟抑郁症脑神经细胞损伤状态,发现目前三类经典抗抑郁剂,包括三环抗抑郁剂地昔帕明（DIM） 0.625-10μmol/L,5-HT重摄取抑制剂氟西丁（FLU）0.625-10μmol/L,单胺氧化酶A抑制剂马氯贝胺（MOC）2.5-40μmol/L对皮质酮损伤的PC12细胞具有显著的保护作用,而抗精神病药氯丙嗪和抗焦虑药地西泮无此作用,DIM 1,5 μmol/L或FLU1,5 μmol/L显著减弱皮质酮0.1 mmol/L处理PC12细胞48h诱导的胞内Ca²⁺超载,进一步研究发现,DIM或FLU 10μmol/L处理PC12细胞48h显著提高NGF mRNA的表达水平。结论:尽管各类抗抑郁剂结构迥异,但细胞保护作用可能是其共同作用通路,而减弱胞内Ca²⁺超载和提高NGF等神经营养因子的表达是抗抑郁药的细胞保护作用机制之一。更多还原

【Abstract】 AIM: To explore the possible common action mechanism of antidepressants. METHODS: The cell viability was detected by MTT assay. The intracellular Ca²⁺ concentration([Ca²⁺]_i) was measured by Fura 2-AM fluorescence labeling assay. Using RT-PCR, the mRNA level of nerve growth factor（NGF） was also detected. RESULTS: High concentration of corticosterone（0.2 mmol/L） was incubated with PC 12 cells to simulate the lesion state of brain neurons in depressive illness. Three main kinds of antidepressants used in clinic [（1） tricyclic antidepressants（TCAs）, such as desipramine（DIM） 0.625-10 μmol/L; （2） selective serotonin reuptake inhibitors（SSRIs）, such as fluoxetine（FLU） 0.625-10 μmol/L; （3） monoamine oxidase inhibitors（MAOIs）, such as moclobemide（MOC） 2.5-40 μmol/L] protected cells from the lesion induced by corticosterone. While antipsychotic drug chlorpromazine oranxiolytic agent diazepam 0.4-50μmol/L had no such effect. Moreover, DIM 1, 5μmol/L or FLU 1, 5μmol/L attenuated the[Ca²⁺]_i overload induced by corticosterone 0.1 mmol/L for 48 h in PC 12 cells. Furthermore, treatment with DIM or FLU 10μmol/L for 48 h elevated the NGF mRNA expression in PC12 cells. CONCLUSION: Despite a remarkable structural diversity, the cytoprotective effect can be viewed as the common action pathway of the antidepressants. Moreover, attenuation of the intracellular Ca²⁺ overload and elevation of neurotrophic factor（such as NGF） expression is one of the mechanisms of cytoprotective effect of antidepressants.更多还原