左旋多巴和多巴胺对PC12细胞的毒性及其他抗帕金森病药物的神经保护作用

Toxicity of levodopa and dopamine on PC12 Cells and neuroprotective effect of several anti-Parkinson drugs on the toxicity

目的 研究左旋多巴和多巴胺对PC12细胞的毒性作用以及抗帕金森病 (PD)药物的神经保护作用。 方法 通过体外大鼠嗜铬细胞瘤PC12细胞培养 ,采用溴化 3(4 ,5 二甲基噻唑基 2 ) 2 ,5 二苯基四唑 (MTT)细胞活性检测和流式细胞仪观察不同剂量左旋多巴和多巴胺对PC12细胞的毒性作用 ,以及抗PD药物 (金刚烷胺、培高利特和司来吉兰 )能否拮抗左旋多巴和多巴胺的细胞毒性。 结果 MTT显示左旋多巴和多巴胺使PC12细胞活性降低 ,与剂量、时间相关 (P <0 0 1) ;流式细胞仪显示左旋多巴和多巴胺使PC12细胞发生凋亡 ,呈剂量依赖性 (P <0 0 1)。金刚烷胺、培高利特和司来吉兰均能保护PC12细胞活性 ,免受左旋多巴和多巴胺的影响 (P <0 0 1) ,并能抑制左旋多巴和多巴胺引起的PC12细胞凋亡 (P <0 0 5 )。 结论 大剂量左旋多巴和多巴胺对PC12细胞产生毒性损害 ,金刚烷胺、培高利特和司来吉兰能拮抗左旋多巴和多巴胺对PC12细胞的毒性效应 ,具有神经保护作用。

Objective To investigate the toxicity of levodopa and dopamine on PC12 cells and neuroprotection of several anti-Parkinson drugs i.e. amantadine,pergolide and selegiline. Methods The possible cytotoxicity of levodopa and dopamine at different dosage on rat pheochromocytoma PC12 cells and the effects of some anti-Parkinson drugs (amantadine,pergolide and selegiline) on levodopa- or dopamine-induced cytotoxicity were determined by MTT assay and flow cytometry. Results There was a concentration- and time-dependent decrease in cell viability and a concentration-dependent increase in apoptotic cells induced by levodopa and dopamine ( P <0.01). The cytotoxicity induced by levodopa and dopamine could be blocked by amantadine,pergolide and selegiline at optimal concentrations ( P <0.01). In addition,these anti-Parkinson drugs significantly inhibited apoptotic production caused by levodopa and dopamine ( P <0.05). Conclusions Levodopa and dopamine(≥1 nmol/L) are neurotoxic for PC12 cells,and the anti-Parkinson drugs tested could inhibit the levodopa-and dopamine-induced toxicity.