α-苯基-N-叔丁基硝酮对MPP^+/MPTP诱发帕金森病模型的神经保护作用

Study on neuroprotection of α-phenyl-N-tert-butyl nitrone for anti-Parkinson's disease in vitro and in vivo

目的探讨抗氧化剂α-苯基-N-叔丁基硝酮(PBN)对MPP^+/MPTP诱发帕金森病模型的神经保护作用。方法通过化学方法诱导自由基生成造成神经元损伤,分别在MPP^+诱导损伤的细胞模型和MPTP诱导的动物模型中研究PBN的神经保护作用。结果 PBN对非细胞体系产生的自由基表现明显的清除作用,能明显抑制MPP^+诱导的SHSY5Y细胞内自由基生成,提高神经元的存活率。在MPTP诱导的小鼠帕金森病模型中,PBN能明显提高黑质致密部酪氨酸羟化酶阳性细胞数目,增加黑质致密部Nrf2和HO-1蛋白的表达,提高纹状体内DA及其代谢产物含量。结论PBN对MPP^+/MPTP诱发帕金森病模型具有良好的神经保护作用。

Aim To discuss the neuroprotection of antioxidant α-phenyl-N-tert-butyl nitrone（ PBN） in Parkinson＇s disease（ PD） model.Methods The neuroprotective effects of PBN was explored on 1-methyl-4-phenylpyridinium/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（ MPP~＋/MPTP） induced PD models through a chemical releasing of free radicals in neurons and in vivo.Results PBN significantly scavenged chemical derived free radicals,reduced MPP~＋induced SH-SY5Y injury and enhanced neurons＇ viability.In MPTP induced PD model,PBN significantly enhanced the number of tyrosine hydroxylase（ TH）-positive dopamine（ DA） neurons in the substantia nigra,restored the expression of Nrf2 and HO-1,and raised striatal contents of DA and its metabolites.Conclusion PBN has a potent neuroprotective effect against MPP~＋/MPTP induced PD models.