【摘要】 [目的]研究c-Jun氨基端激酶(c-Jun N-terminal protein kinase,JNK)在1-甲基4-苯基-1,2,3,6-四氢吡啶(MPTP)所致小鼠帕金森病(Parkinson’s disease,PD)模型中对PD黑质多巴胺(Dopamine,DA)能神经元丢失的可能机制以及人参皂甙Rg1的神经保护作用。[方法]采用神经毒素MPTP制备PD小鼠模型,免疫组织化学法与蛋白印迹法观察各组小鼠黑质酪氨酸羟化酶(TH)和磷酸化c-Jun(p-c-jun)表达变化;原位末端标记法(TUNEL)观察黑质细胞凋亡数量变化。[结果]与对照组相比,模型组小鼠黑质致密带TH阳性神经元显著减少约55%(P﹤0.01),p-c-jun表达水平亦明显升高,黑质神经元TUNEL阳性细胞数量增高;人参皂甙Rg1干预组黑质TH阳性神经元细胞丢失明显减轻31%(P﹤0.01),p-c-jun表达水平明显下降,黑质神经元TUNEL阳性细胞数量显著减少。[结论]JNK通路可能通过凋亡途径参与模型小鼠黑质多巴胺能神经元丢失过程;人参皂甙Rg1可在一定程度上阻抑黑质区JNK信号通路,减轻MPTP诱导的PD小鼠黑质DA能神经元凋亡;人参皂甙Rg1对帕金森病小鼠具有一定的神经保护作用。更多还原

【Abstract】 [Objective]To investigate the effect of c-Jun N-terminal protein kinase(JNK) on the possible mechanism of the loss of dopaminergic nigral nurons apoptosis of Parkinson’s disease(PD) model induced by 1-Methy-4-phenyl-1,2,3,6-tetrahydropyri-dine(MPTP) ,and its neuroprotective effect on the Ginsenoside Rg1.[Methods]Chronic PD model was produced by MPTP,and the expression and change of tyrosine hydroxylase(TH) and phosphorylation c-Jun(p-c-jun) in mice were observed by immunohistochemistry and Western blotting.Apoptotic cell number was observed by TdT-mediated dUTP-biotin nick end labeling(TUNEL) .[Results]When compared with control group,the number of TH-positive neurons in model group was significantly decreased by almost 55%(P﹤0.01) ,the expression levels of p-c-jun in ventral midbrain significantly elevated(P﹤0.01) and the numbers of TUNEL positive cells in SN significantly increased(P﹤0.01) ;,Mice treated with Ginsenoside Rg1,the number of TH-positive neurons in SN was decreased by 31% when compared with the control group(P﹤0.01) .The expression of p-c-Jun was significantly decreased,and the TUNEL positive cells in SN significantly decreased(P﹤0.01) .[Conclusion]The path of signal transduction of JNK maybe participate in the loss of the dopaminergic neurons by inducing apoptosis of substantia nigra neuronsin PD mouse model;Ginsenoside-Rg1 can restrain the JNK signaling path in substantia nigra district to some extent,and decrease the apoptosis of dopaminergic nigral nurons of mice with PD induced by MPTP,Ginsenoside Rg1 has neuroprotective effect on mice with PD.更多还原