JNK通路可能介导MPTP诱导的黑质神经元凋亡  

JNK Signaling Pathway Mediate MPTP-induced Apoptosis in Substantia Nigra Neurons

作　　者：周宜灿[1] 陈晓春[1] 朱元贵[1] 方芳[1] 陈丽敏[1] 陈滢[1] 

机构地区：[1]福建医科大学附属协和医院,福建省老年医学研究所,福州350001

出　　处：《福建医科大学学报》2003年第2期125-127,F002,共4页Journal of Fujian Medical University

基　　金：福建省科技厅科研基金资助项目 ( 2 0 0 1Z0 3 7) ;福建省教育厅科研基金资助项目 ( JA0 2 2 19)

摘　　要：目的　探讨氧化应激激活的 c- jun NH2 - term inal kinase(JNK)细胞凋亡通路在 1-甲基 - 4 -苯基 - 1,2 ,3,6 -四氢吡啶 (MPTP)诱导帕金森病 (PD)小鼠黑质神经元凋亡中的可能作用。　方法　采用 MPTP制备 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 ,尼氏体染色和酪氨酸羟化酶 (TH)免疫组织化学染色观察黑质神经元的损害情况 ,原位缺口末端标记 (TUNEL )染色和活化型 Caspase 3免疫组织化学染色观察黑质神经元的凋亡情况 ,同时采用蛋白免疫印迹法检测磷酸化 JNK及磷酸化 c- jun蛋白表达水平。　结果　MPTP诱导的 PD小鼠黑质区域 GSH浓度明显降低 ,SOD活力明显升高 ,黑质致密带尼氏体阳性神经元和 TH阳性神经元显著脱失 ,磷酸化 JNK及磷酸化 c- jun蛋白表达水平上升 ,同时活化型 Caspase 3表达阳性细胞增多 ,黑质神经元 TUNEL 染色的阳性率增高。　结论　 MPTP可诱导小鼠黑质神经元凋亡 ,机制与增强氧化应激并激活 JNK细胞凋亡通路有关。Objective To explore the possible role of c\|jun NH\-2\|terminal kinase(JNK) in induction of 1\|methyl\|4\|phenyl\|1,2,3,6\|tetrahydropyridine(MPTP) in apoptosis of substantia nigra neurons Parkinson's disease(PD) mouse model. Methods C57BL mice were administrated with MPTP to produce PD model. Biochemical techniques were used to detect the concentration of GSH and the activity of SOD in substantia nigra. Nissl staining, tyrosine hydroxylase(TH) immunohistochemistry staining, cleaved caspase 3 immunostaining and TUNEL staining were used to observe the changes of nigra neurons. Meanwhile, Western blot was used to detect the phosphorylated protein of JNK and c\|jun in substantia nigra. Results MPTP increase the concentration of GSH and decrease the activity of SOD in substantia nigra, result in the significant loss of Nissl staining neurons and TH\|positive neurons, lead to the phosphorylation of JNK and c\|jun, and increase the percentage of cleaved caspase 3 and TUNEL\|positive cell. Conclusion MPTP may induce apoptosis of substantia nigra neurons in PD mouse model. The mechanism is ascribed to enhancing oxidative\|stress and sequentially activating of JNK signaling cascade.

关 键 词：黑质 神经元 细胞凋亡 氧化性应激 蛋白激酶类 基因 jun 

分 类 号：R742.5[医药卫生—神经病学与精神病学]