N-乙酰半胱氨酸防止帕金森病鼠黑质神经元凋亡

N-acetylcystein protects dopaminergic neurons of the substantia nigra from apoptosis in the PD-mouse model

目的 :研究N 乙酰半胱氨酸 (N acetylcystein ,NAC)对 1 甲基 4 苯基 1,2 ,3,6 四氢吡啶 (1 methyl 4 phenyl 1,2 ,3,6 tetrahydropyridine ,MPTP)诱导的帕金森病小鼠黑质神经元凋亡的保护机制。 方法 :采用MPTP制备帕金森病 (Parkinsondisease,PD)小鼠模型 ,应用生化技术检测黑质区域谷胱甘肽 (GSH)浓度及超氧化物歧化酶 (SOD)活力 ,用尼氏 (Nissl)染色、TH组化染色、活化型Caspase 3组化染色及TUNEL染色观察黑质神经元的损害情况 ,并计算神经元的凋亡率 ,同时应用蛋白免疫印迹法检测黑质神经元磷酸化JNK及磷酸化c Jun蛋白表达水平。另经NAC预处理该模型后 ,对上述指标进行检测。结果 :NAC预处理能提高黑质区域GSH的浓度及降低SOD活力 ,减轻PD鼠黑质致密带Nissl阳性神经元和TH阳性神经元的脱失现象 ,减少磷酸化JNK及磷酸化c Jun蛋白表达水平 ,使活化型Caspase 3表达减少并降低黑质神经元的凋亡率。结论 :NAC能减少MPTP诱导的小鼠黑质神经元凋亡 ,其机制与抗氧化及阻断JNK细胞凋亡通路的激活有关。

Objective: To explore the protective effect of N-acetylcystein (NAC) against 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) induced apoptosis of substantia nigra neurons. Methods: MPTP was administrated (sc) to C57BL mice to produce PD mouse model. NAC was given (sc) 3 d prior to MPTP injection. Western bloting was used to detect the concentration of GSH and the vitality of SOD in substantia nigra. Immunohistochemistry for tyrosinehydroxythase (TH),cleaved caspase 3 and TUNEL were used to observe the survival of nigra neurons. Meanwhile,Western bloting was used to detect the phosphorylated protein of JNK and c-Jun in substantia nigra. Results: Pretreatment with NAC could increase the concentration of GSH,decrease the vitality of SOD,prevent the loss of TH-positive neurons,inhibit JNK and c-Jun phosphorylation and decrease the proportin of cleaved caspase 3 and TUNEL-positive cell in substantia nigra. Conclusion: NAC can attenuate MPTP-induced apoptosis of substantia nigra neurons through down-regulating oxidative stress and blocking JNK signaling cascade.