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利噜唑拮抗左旋多巴和多巴胺对中脑原代细胞的毒性作用

Riluzole Prevents Levodopa and Dopamine-Induced Toxicity in Primary Rat Mesencephalic Cells
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摘要 目的:研究左旋多巴(L-DOPA)和多巴胺(DA)对大鼠胚胎中脑原代细胞的毒性损害以及利噜唑拮抗L-DOPA和DA的毒性作用。方法:通过体外大鼠胚胎中脑原代细胞培养,采用MTT细胞活性和[~3H]DA摄取率检测中脑原代细胞的存活数和DA能神经元的[~3H]DA摄取功能。结果:当L-DOPA和DA浓度增至500 μmol·L^(-1)时,细胞存活率明显下降(P<0.05),均呈剂量依赖性。当L-DOPA和DA浓度分别增至1mmol·L^(-1)和200μmol·L^(-1)时,[~3H]DA摄取率明显下降(P<0.05),均呈剂量依赖性。利噜唑2~10μmol·L^(-1)能抑制L-DOPA和DA对细胞存活率和[~3H]DA摄取率的影响(P<0.05)。结论:大剂量L-DOPA和DA(≥500 μmol·L^(-1))对中脑原代细胞产生毒性损害,利噜唑能拮抗L-DOPA和DA对中脑原代细胞的毒性效应,具有神经保护作用。 Aim: To investigatte the toxicity of levodopa and dopamine on the primary rat mesencephalic cells and also the neuroprotection of riluzole on the levodopa and dopamine-induced toxicity. Methods: The survival of primary rat mesencephalic cells was measured by MTT assay, and the function of dopaminergic neurons was detected by [3H]DA uptake measurement through the in vitro cell culture. Results: The cell viability and [3H]DA uptake were decreased at high concentration of levodopa and dopamine in dose dependent manner (P < 0.05- P < 0.01). The levodopa and dopamine-induced reduction of cell viability and [3H] DA uptake was blocked by riluzole at optimal concentrations (2-10 μmol·L-1) ( P < 0.05). Conclusion: Levodopa and dopamine (≥500 μmnol·L-1 ) were neurotoxic to primary rat mesencephalic cells, and riluzole can inhibit the levodopa and dopamine-induced toxicity as a neuroprotective effect.
出处 《中国临床神经科学》 2003年第1期30-33,共4页 Chinese Journal of Clinical Neurosciences
基金 国家重点基础研究规划"脑功能和脑重大疾病的基础研究"项目(G1999054008) 国家科委"九五"攻关项目(96-906-05-08) 卫生部科学研究基金(98-1-319) 上海市卫生系统百名跨世纪优秀学科带头人培养计划(97BR001)
关键词 左旋多巴 多巴胺 毒性作用 利噜唑 神经保护作用 帕金森病 levodopa dopamine toricity riluzole neuroprotection
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