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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Ca~(2+)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Ca~(2+)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Ca~(2+)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。
Objective: To explore the possible mechanism of action of antidepressants. Methods: The cell viability was detected by MTT colorimetric assay. The intracellular Ca 2+ concentration was determined by Fura 2-AM fluorescence labeling method. The level of NGF mRNA was detected by RT-PCR. Results: PC12 cells were treated with 0.2 mmol / L corticosterone for 48 h to simulate the neuronal damage in depression. Three classes of classic antidepressants were found, including the tricyclic antidepressant desipramine (DIM) 0.625-10 μmol / L, 0.625-10μmol / L of 5-HT reuptake inhibitor (FLU) and 2.5-40μmol / L of monoamine oxidase A (MOC) had a significant protective effect on corticosterone-injured PC12 cells , While antipsychotic chlorpromazine and anti-anxiety drugs diazepam did not have this effect, DIM 1,5 μmol / L or FLU 1, 5 μmol / L significantly reduced the cortisone 0.1 mmol / L treatment of PC12 cells 48h induced intracellular Ca ~ (2+) overload, further study found that DIM or FLU 10μmol / L treatment of PC12 cells 48h significantly increased NGF mRNA expression levels. CONCLUSIONS: Although all kinds of antidepressants have different structures, the protective effect may be their common pathway. However, decreasing the intracellular calcium overload and increasing the expression of NGF and other neurotrophic factors are the cytoprotective effects of antidepressants One of the mechanisms.