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首页> 外文期刊>Acta Pharmacologica Sinica >Cytoprotective effect is one of common action pathways for antidepressants
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Cytoprotective effect is one of common action pathways for antidepressants

机译:细胞保护作用是抗抑郁药的常见作用途径之一

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AIM: To explore the possible common action mechanism of antidepressants. METHODS: The cell viability was detected by MTT assay. The intracellular Ca~(2+) concentration ([Ca~(2+)]_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 or anxiolytic agent diazepam 0.4-50 μmol/L had no such effect. Moreover, DIM 1, 5 umol/L or FLU 1, 5 μmol/L attenuated the [Ca~(2+)]_i overload induced by corticosterone 0.1 mmol/L for 48 h in PC12 cells. Furthermore, treatment with DIM or FLU 10 μmol/L for 48 h elevated the NGF mRNA expression in PC 12 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 Ca~(2+) overload and elevation of neurotrophic factor (such as NGF) expression is one of the mechanisms of cytoprotective effect of antidepressants.
机译:目的:探讨抗抑郁药可能的共同作用机制。方法:采用MTT法检测细胞活力。通过Fura 2-AM荧光标记测定法测量细胞内Ca〜(2+)浓度([Ca〜(2 +)] _ i)。使用RT-PCR,还检测了神经生长因子(NGF)的mRNA水平。结果:将高浓度的皮质酮(0.2 mmol / L)与PC 12细胞孵育,以模拟抑郁症患者脑神经元的病变状态。临床上使用的三种主要抗抑郁药[(1)三环类抗抑郁药(TCA),例如地昔帕明(DIM)0.625-10μmol/ L; (2)选择性5-羟色胺再摄取抑制剂(SSRIs),例如氟西汀(FLU)0.625-10μmol/ L; (3)单胺氧化酶抑制剂(MAOIs),例如莫氯贝米(MOC)2.5-40μmol/ L]可保护细胞免受皮质酮诱导的损伤。抗精神病药氯丙嗪或抗焦虑药地西epa 0.4-50μmol/ L无此作用。此外,DIM 1、5 umol / L或FLU 1、5μmol/ L减弱了皮质醇0.1 mmol / L在PC12细胞中诱导的[Ca〜(2 +)] _ i超负荷48小时。此外,用DIM或FLU 10μmol/ L处理48小时可提高PC 12细胞中NGF mRNA的表达。结论:尽管存在显着的结构多样性,但细胞保护作用可被视为抗抑郁药的共同作用途径。此外,细胞内Ca〜(2+)超负荷的减弱和神经营养因子(如NGF)表达的升高是抗抑郁药细胞保护作用的机制之一。

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