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目的 :研究特异性JNK抑制剂SP6 0 0 1 2 5对MPP+ 诱导凋亡的多巴胺能神经元的保护作用。方法 :体外培养多巴胺能神经元 ,以MPP+ 引起胎鼠腹侧中脑神经元损伤作为PD的细胞模型 ,免疫细胞化学方法检测多巴胺能神经元的凋亡情况 ,免疫荧光双染色的方法检测多巴胺能神经元内磷酸化c -Jun的水平。结果 :浓度为 1 0 μmol/LMPP+ 可以激活多巴胺神经元内JNK而使c -Jun磷酸化 ,从而诱导神经元发生典型的凋亡 ,使TH -阳性细胞的数目减少 ,胞浆体积减小。而SP6 0 0 1 2 5能够通过抑制c -Jun磷酸化而减少神经元的凋亡 ,使TH -阳性细胞数目显著增加 ,对MPP+ 诱发的神经元凋亡具有明显的保护作用。结论 :SP6 0 0 1 2 5可以通过特异性地抑制JNK活性而对MPP+ 诱导凋亡的多巴胺神经元发挥保护作用 ;同时也提示JNK可以作为药物作用的新靶点 ,这就为研究开发抗PD药物提供了新思路、新方法和新策略
AIM: To investigate the protective effect of SP6 0 0 1 2 5, a specific JNK inhibitor, on dopaminergic neurons induced by MPP +. Methods: Dopaminergic neurons were cultured in vitro. MPP + was used to induce the injury of ventral midbrain neurons in fetal rats as a model of PD. The apoptosis of dopaminergic neurons was detected by immunocytochemistry. The dopaminergic Neuronal phosphorylation of c-Jun levels. Results: The concentration of 10 μmol / L MPP + could activate JNK in dopaminergic neurons to phosphorylate c-Jun and induce typical apoptosis in neurons. The number of TH - positive cells and the volume of cytoplasm decreased. However, SP6 0 0 1 2 5 could reduce neuronal apoptosis by inhibiting c-Jun phosphorylation, significantly increase the number of TH-positive cells and significantly protect MPP + -induced neuronal apoptosis. Conclusion: SP6 0 0 1 2 5 can protect MPA + -induced dopaminergic neurons by specifically inhibiting JNK activity. It also suggests that JNK can be used as a new target of drug action, Drugs provide new ideas, new methods and new strategies