摘要
目的在体外细胞水平探讨阿姆西汀的抗抑郁作用机制。方法分离培养新生大鼠海马神经前体细胞,采用ATP生物发光法检测阿姆西汀对神经前体细胞增殖的影响;以皮质酮损伤原代培养大鼠海马神经元为模型,检测阿姆西汀的细胞保护作用;并采用PKA特异性抑制剂H89探讨其可能的作用机制。结果 0.5~2.5μmol/L阿姆西汀可浓度依赖性地促进神经前体细胞的增殖;100μmol/L皮质酮对神经元具有明显的损伤作用,2.5,5μmol/L阿姆西汀可显著逆转皮质酮的损伤作用,度洛西汀具有同样的作用;并且10μmol/L H89可取消以上作用。结论阿姆西汀在体外具有促进神经元再生和对神经元损伤的保护作用,这可能是阿姆西汀抗抑郁效应的重要细胞机制,且这一作用可能与c AMP-PKA-CREB通路有关。
Objective To explore the mechanisms underlying the antidepressant-like effects of ammuxetine（Amx） in vitro.Methods Neural progenitor cells were separated and cultured to investigate the effect of Amx on neural progenitor cells proliferation.Primary hippocampus neurons were incubated with corticosterone（100 μmol / L） in the absence or presence of Amx to investigate its cytoprotective effect.The cell viability was measured by ATP-luminescent cell viability assay.Additionally,H89（PKA specific inhibitor） was used to investigate the related signaling pathway underlying these effects.Results Amx（0.5-2.5 μmol / L） significantly increased the proliferation of neural progenitor cells in a dose-dependent manner.Incubation with corticosterone（100 μmol / L） induced significant lesion in primary culture of hippocampal neurons,and Amx（2.5 and 5 μmol / L） could significantly attenuate the lesion.Duloxetine produced similar effects.Furthermore,these effects of Amx could be abolished by H89（10 μmol / L）.Conclusion Amx can increase neuronogenesis and protect hippocampus neurons from the lesion induced by corticosterone in vitro,which may be the important cellular mechanism underlying the antidepressant-like effects of Amx.Moreover,these effects may be related to c AMP-PKA-CREB signaling pathway.
出处
《军事医学》
CAS
CSCD
北大核心
2015年第1期18-21,共4页
Military Medical Sciences
基金
国家科技重大专项资助项目(2012ZX09102101-004)
国家自然科学基金资助项目(81274117
30901975
81302761)
