磷酸化ERK1/2对MPTP帕金森病模型小鼠黑质NF-κB p65表达的影响

Effect of phosphorylated-ERK1/2 on NF-κB p65 expression in substantia nigra of mice with MPTP-induced Parkinson's disease

目的研究磷酸化ERK1/2(p-ERK1/2)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)所致帕金森病(PD)小鼠模型黑质NF-κB p65的表达调控作用。方法应用MPTP建立PD小鼠模型,观察小鼠行为学变化;采用免疫组织化学和免疫蛋白印迹法观察小鼠黑质抗酪氨酸羟化酶(TH)、NF-κB p65及p-ERK1/2的表达变化;并观察给予ERK特异性抑制剂U0126后对上述变化的影响。结果模型组小鼠于MPTP第3次注射后1h,黑质区p-ERK1/2阳性细胞数多于NF-κB p65阳性细胞,第5次注射后24h,NF-κB阳性细胞增多,p-ERK1/2阳性细胞减少,同时伴有TH阳性神经元丢失;给予ERK特异性抑制剂U0126后,上述变化明显减轻。结论在MPTP所致PD小鼠模型中ERK1/2信号通路可能通过调控NF-κB p65活化从而导致多巴胺能神经元变性丢失。

Objective To investigate the effect of phospholated-ERK1/2 on NF-κB p65 expression in the substania nigra（SN） of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced mouse model of Parkinson＇s disease（PD）. Methods PD mouse model was induced by MPTP and the behavior of mouse was observed.Immunohistochemistry and Western blotting analysis were used to observe the changes in expression of tyrosine hydroxylase（TH）,NF-κB p65 and p-ERK1/2 in the SN of midbrain.Meanwhile,the above changes were also observed after treatment with U0126,a specific inhibitor of ERK.Results 1 h after the third MPTP administration,there were much more p-ERK1/2 positive cells than NF-κB p65 positive cells in the SN.24 h after the fifth injection of MPTP,NF-κB p65 positive cells were significantly increased and p-ERK1/2 positive cells were decreased,accompanied by marked loss of TH positive neurons.The above changes were greatly alleviated in animals treated with U0126.Conclusion ERK1/2 pathway may regulate NF-κB p65 activation in MPTP-induced mouse model of Parkinson＇s disease,which leads to loss of dopamine neurons.