地昔帕明和氟西汀拮抗5,7-二羟色胺对海马和皮质神经元的损伤(英文)

Desipramine and fluoxetine antagonized 5,7-dihydroxytryptamine-induced lesion on rat hippocampal and cortical neurons

目的:评价抗抑郁剂地昔帕明和氟西汀对5,7-二羟色胺损伤神经元的拮抗作用。方法:原代培养10d的大鼠海马和皮层细胞加入不同浓度的地昔帕明和氟西汀作用30min后,用5,7-二羟色胺600μmol·L^(-1)损伤4h,MTT法结合形态学观察判断药物的保护作用。结果:地昔帕明和氟西汀对神经元损伤具有显著拮抗作用,剂量范围分别为0.8-10μmol·L^(-1)和0.04-0.6μmol·L^(-1)。结论:地昔帕明和氟西汀对5,7-二羟色胺的神经元损伤具有显著拮抗作用,氟西汀效价高于地昔帕明(约一个数量级)。两种抗抑郁剂对神经元的保护作用可能是它们抗抑郁作用的机制之一。

AIM: To assess the protective effect of desipramine (Des) and fluoxetine (Flu) on the neurons against the lesion induced by a selective serotonergic neurotoxin in vitro. METHODS: The 10-day cultured primary neurons of hippocampus and cortex of rat was exposed to 5, 7-dihydroxytryptamine (5,7-DHT) to determine the optimal lesion concentration and duration. Before exposing to 5, 7-DHT, Des and Flu was added to the medium for 30 min to observe the protective effects. RESULTS: The optimal concentration and duration for 5, 7-DHT was 600 μmol · L-1 and 4 h, respectively. Both Des and Flu showed a protective effect in the dose range of 0.8 μmol ·L-1 to 10 μmol · L-1 and 0.04 μmol·L-1 to 0.6 μmol·L-1, respectively, when the neurons were injured by 5,7-DHT 600 μmol·L-1 for 4 h. Flu showed a higher efficacy than Des. Both exhibited a more powerful protective effect on the hippocampal neuron than on the cortical neuron. CONCLUSION: The antidepressant effect of Des and Flu was attributed to their protective effect on the injured serotonergic neuron of the hippocampus and the cortex.