N-乙酰半胱氨酸防止帕金森病鼠黑质神经元凋亡

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-phe-ny-1．1，2，3，6-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(Parkinson disease，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Caspase3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Caspase3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。

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

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.