| 摘要: |
| 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1 h, 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24 h,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。 |
| 关键词: 帕金森病 MPTP中毒 磷酸化 ERK1/2 NF-κB p65 黑质 |
| DOI：10.3724/SP.J.1008.2011.01176 |
| 投稿时间：2011-05-10修订日期：2011-09-27 |
| 基金项目:河北省自然科学基金(C2004000689),河北省博士基金(05547008D-4),河北省科学技术与社会发展计划(04276135). |
|
| Effect of phosphorylated-ERK1/2 on NF-κB p65 expression in substantia nigra of mice with MPTP-induced Parkinson’s disease |
| ZHANG Zuo-feng,MENG Guo-guang,ZHOU Hong-xia,WEI Zi-feng,ZHANG Yu-xin* |
(Department of Anatomy, Basic Medical College of Hebei Union University, Tangshan 063000, Hebei, China
*Corresponding author.) |
| Abstract: |
| 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. |
| Key words: Parkinson disease MPTP poisoning p-ERK1/2 NF-κB p65 substantia nigra |
