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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 effects of phosphorylated ERK1 / 2 (p-ERK1 / 2) on Parkinson’s disease (PD) mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Regulation of substantia nigra NF-κB p65 expression. Methods PD mice model was established by MPTP to observe the behavioral changes in mice. Immunohistochemistry and Western blotting were used to detect the tyrosine hydroxylase (TH), NF-κB p65 and p-ERK1 / 2 expression changes; and observed after given ERK specific inhibitor U0126 on the above changes. Results The number of p-ERK1 / 2 positive cells in the substantia nigra was higher than that of NF-κB p65 positive cells 1 h after the third injection of MPTP. The number of NF- ERK1 / 2 positive cells decreased, accompanied by the loss of TH positive neurons; given ERK specific inhibitor U0126, the change was significantly reduced. Conclusion ERK1 / 2 signaling pathway may be involved in the deregulation of dopaminergic neurons through the regulation of NF-κB p65 activation in MPTP-induced PD mice.