左旋多巴对胶质细胞培养液中自由基系统动态平衡的影响

Effect of L-DOPA on dynamical balance of free radicals in mesencephalic cell cultures

目的 通过体外实验探讨左旋多巴 (L- DOPA)在胶质细胞培养液中对自由基系统动态平衡的影响 ,以进一步明确 L- DOPA在治疗帕金森氏病时 ,可能加速其进展的的机制。方法 将 L- DOPA5 0 μm ol、10 0 μmol、5 0 0 μmol加入含有胶质细胞的中脑培养液中 ,分别在 4 h、2 4 h、4 8h和 72 h时间点取标本 ,设空白对照组 ,测定谷胱甘肽 (GSH)的含量、谷胱甘肽过氧化物酶 (GSH- Px)的活性、超氧歧化酶 (SOD)的活力及丙二醛 (MDA)的水平。结果 L- DOPA10 0 μmol2 4 h、4 8h、72 h和 5 0 0 μmol各个时间点 GSH的含量、GSH- Px的活性、SOD的活力较对照组显著的下降 (P<0 .0 5～ 0 .0 1) ,MDA的水平显著的升高 (P<0 .0 5～ 0 .0 1)。结论 L- DOPA自身氧化产生大量的自由基 ,消耗自由基清除剂 ,使自由基清除能力下降 ,破坏胶质细胞培养液中自由基系统的动态平衡 ,大量的毒性物质可致神经元变性 ,其作用有浓度和时间依赖性。

Objective To evaluate the effect of L-DOPA on dynamical balance of free radicals in glial cell cultures by means of in vitro for understanding further mechanisms of L-DOPA accelerating the rate of progression of Parkinson's disease.Methods Glia-containing mesencephalic cultures were treated with L-DOPA(50μmol、100μmol、500μmol),glutathione (GSH) content,glutathione peroxidase(GSH-Px) activity, superoxide dismutase(SOD) activity,malondialdehyde(MDA) level were determined after 4h,24h,48h and 72h.Results shown that L-DOPA had significant effect on dynamical balance of free redicals at 24h,48h,72h after treated 100μmol and at 4h,24h,48h,72h aftertreated 500μmol,that is,GSH content,GSH-Px activity,SOD activity decreased markedly(P<0.05~0.01) and MDA levels increased markedly(P<0.05～0.01) comparison with controls.Conclusions In vitro autoxidation of L-DOPA form a great quantity free redicals which consumed antioxidants.Dynamical balance of free radicals in glial cell cultures is destroyed.Toxicants resulted in degeneration of neurons.There are concentration- and time-dependent effects of L-DOPA in this process.