摘要
目的 本研究观察了胍丁胺 (agmatine,AG)的抗抑郁作用 ,并初步探讨其可能的作用机理。方法与结果 在小鼠悬尾实验及强迫游泳实验中 ,首次发现灌胃给予AG 4 0 ,80mg·kg-1或皮下注射 2 0mg·kg-1可以显著缩短悬尾或强迫游泳不动时间。同样 ,AG 10mg·kg-1灌胃或皮下注射 1.2 5～ 5mg·kg-1显著缩短大鼠强迫游泳不动时间。MTT比色法及LDH法的研究表明 ,AG1～ 10 0 μmol·L-1,去甲丙米嗪 (DIM)及NMDA受体拮抗剂MK80 1均可以对抗NMDA 30 0 μmol·L-1诱导的PC12细胞损伤。同时运用fura- 2 /AM荧光标记法发现 ,AG 1,10 μmol·L-1或DIM 1,5 μmol·L-1均减轻NMDA 2 0 0 μmol·L-1诱导的PC12细胞内Ca2 + 超载。结论 AG具有明确的抗抑郁作用 ,抑制NMDA诱导的细胞损伤并减弱细胞内Ca2 + 超载可能是其抗抑郁作用机理之一。
Aim In mammalian brain,agmatine (AG) is regarded as an endogenous neurotransmitter and/or neuromodulator. In this study, the antidepressant effect of AG and the possible mechanism were observed.Methods and Results AG at the doses 40,80 mg·kg -1 (ig) reduced immobility time in tail suspension test and forced swim test in mice or at the dose 20mg·kg -1 (ig) in forced swim test.AG also reduced the immobility time at the dose 10 mg·kg -1 (ig) or 1.25,2.5,5mg·kg -1 (sc) in forced swim test in rats.These results indicated AG possessed antidepressant-like effect.With MTT assay and LDH assay,AG 1,10,100μmol·L -1 or desipramine (DIM) 0.625,2.5,10μmol·L -1 protected PC12 cells from the N-methl-D-aspartare (NMDA) 300μmol·L -1 induced lesion.Furthermore,with the fura-2/AM labeling assay,AG 1,10μmol·L -1 or DIM 1,5μmol·L -1 attenuated the intracellular Ca 2+ overloading in NMDA treated PC12 cells.Conclusion AG possessed antidepressant effect.AG protected PC12 cells from the lesion induced by NMDA and attenuated the NMDA induced intracellular Ca 2+ overloading,which maybe one of the mechanisms of its antidepressant effect.
出处
《解放军药学学报》
CAS
2003年第6期417-420,共4页
Pharmaceutical Journal of Chinese People's Liberation Army
