ERK1/2信号通路对亚急性帕金森病MPTP模型小鼠黑质COX-2,PGE2表达的影响
Effects of ERK1/2 signal pathway on COX-2, PGE2 expression in subacute MPTP-induced mouse model of Parkinson's disease
巨荣凯 1魏子峰 1张作凤 1王茜 1高俊玲 1张宇新1
作者信息
- 1. 华北煤炭医学院解剖学教研室,河北,唐山,063000
- 折叠
摘要
目的:研究ERK1/2信号通路对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)所致帕金森病(PD)小鼠模型中脑黑质环氧合酶2(COX-2)和前列腺素E2(PGE2)的表达调控作用,探讨多巴胺(DA)能神经元变性失活的可能机制.方法:采用MPTP制备亚急性PD小鼠模型,应用免疫组织化学和免疫蛋白印记法观察小鼠黑质酪氨酸羟化酶(TH),COX-2,PGE2以及磷酸化ERK1/2(P-ERK1/2)的表达变化;并观察给予ERK特异性抑制剂U0126对上述因子变化的影响.结果:模型组小鼠出现典型PD样症状,在MPTP第3次注射后1 h,黑质区p-ERK1/2阳性细胞数明显增加,在MPTP第5次注射后24 h,黑质区出现大量COX-2,PGE2阳性细胞,伴有约50%的TH阳性神经元丢失;给予ERK特异性抑制剂U0126后小鼠PD样症状减轻,p-ERK1/2,COX-2,PGE2阳性细胞数明显减少,MPTP第5次注射后24 h,TH阳性细胞数较对照组仅下降25%.结论:ERK1/2通路可能参与调控COX-2及PGE2的表达而在PD发病过程中发挥重要作用,抑制ERK信号通路对帕金森病小鼠具有一定的神经保护作用.
Abstract
AIM: To investigate effects of ERK1/2 signaling pathway on the expression of Cyclooxygenase-2 (COX-2) and Prostaglandin E2(PGE2) in substantia nigra(SN) of the mouse model of Parkinson's disease(PD) induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and to further explore the possible mechanism of dopaminergic neurons loss in PD. METHODS: C57BL/6 mice were administrated with MPTP to produce the subacute PD model, and the mice were observed the behavioral changes. Immunohistochemistry and Western Blot for tyrosine hydroxylase (TH), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and phosphorylated ERK1/2 (p-ERK1/2) were used to observe the changes of positive cell number in SN. After treatment with U0126, a specific inhibitor of ERK, the changes of above-mentioned indices were also observed. RESULTS: Compared with the mice in control group, the mice model appears typical of PD-like symptoms. P-ERK1/2-positive cells increased significantly at 1 h after the 3rd injection of MPTP. The number of COX-2-, PGE2-positive cells was increased obviously as compared with the control group at 24 h after the 5 th injection of MPTP. TH-positive neurons in the PD model group were substantially reduced by about 50%. Treated with U0126, a specific inhibitor of ERK, the performance of PD-like symptoms mitigated, the expression level of p-ERK1/2, COX-2 and PGE2 were significantly decreased in SN compared with mice model group. The number of TH-positive cells in the SN was decreased by only 25% at 24 h after the 5th injection of MPTP. CONCLUSION: ERK1/2 signal pathway may play an important role in regulating COX-2 and PGE2 expression in SN in the early stage of MPTP-induced subacute PD, and inhibition of ERK1/2 signal pathway activity may provide neuroprotective effects for DA neurons in the PD mouse model.
关键词
帕金森病/炎症/磷酸化ERK/环氧合酶-2/前列腺素E2Key words
Parkinson's disease/inflammation/p-ERK1/2/COX-2/PGE2引用本文复制引用
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)
出版年
2009
NETL
NSTL
维普
万方数据