胍丁胺对皮质酮致原代培养大鼠海马神经元损伤的保护作用

目的前期证明胍丁胺作为一种新型神经递质具有抗抑郁作用，本实验通过观察胍丁胺对皮质酮致原代培养海马神经元损伤的保护作用及作用机制，探讨其抗抑郁作用的细胞分子机制。方法体外培养新生大鼠海马神经元，加入不同浓度皮质酮（50～300μmol·L^-1），采用CCK-8试剂盒比色法检测对神经元存活的影响；培养体系内加入胍丁胺，观察对神经元损伤的保护作用；加入H89（PKA特异性抑制剂）或PD98059（MEK特异性抑制剂），观察胍丁胺的神经元保护作用及可能的相关信号通路。结果皮质酮（50～300μmol·L^-1）能够浓度依赖地抑制原代培养海马神经元的存活；同时胍丁胺（5μmol·L^-1）对此损伤具有保护作用；胍丁胺的保护作用可以被H89（20μmol·L^-1）和PD98059（20μmol·L^-1）取消。结论胍丁胺具有神经元保护作用，此作用与cAMP-PKA-CREB通路和MEK-ERK-CREB通路密切相关。

Neuroprotection of Agmatine Against Corticosterone Induced Lesion in Cultured Hippocampal Neurons1

Aim It has been well demonstrated that agmatine has antidepressant-like effect in animal models. In the present study, the neuroprotective effect of agmatine, as well as its related signal pathways, was explored.Methods Primary cultures of hippocampal neurons from neonatal rats were incubated with corticosterone and/or ag- marine, H89 （PKA specific inhibitor）, PD98059 （MEK specific inhibitor）. The cell viability was measured by a colorimetric assay （ CCK-8 kit）. Results Exposure of cultured hippocampal neurons to corticosterone （ 50 - 300 μmol·L^-1 ） produced concentration-dependent neurotoxicity. Agmatine （5 μmol·L^-1） could protect against the neurotoxicity induced by corticosterone and the protection agmarine was fully prevented by H89 （20μmol·L^-1） or PD98059 （20μmol·L^-1）. Conclusion Agmarine has neuroprotective effect against corticosterone induced neurotoxicity in vitro and this effect is mediated through cAMP-PKA-CREB and MEK-ERK-CREB pathways.