P38MAPK对帕金森病MPTP模型小鼠NF-κB和COX-2调控的研究  

Role of P38 MAPK in regulating expression of NF-κB and COX-2 in substantia-nigra of MPTP Parkinson's disease mice model

作　　者：王茜[1] 张辉[2] 张作凤[1] 魏子峰[1] 王永生[1] 周洪霞[1] 张宇新[1] 

机构地区：[1]河北联合大学基础医学院人体解剖学系,河北唐山063000 [2]唐山市第二医院关节科,河北唐山063000

出　　处：《中国现代医学杂志》2012年第28期15-20,共6页China Journal of Modern Medicine

基　　金：河北省自然科学基金(No:C2004000689);河北省博士基金(No:05547008D-4);河北省科学技术与社会发展计划项目(No:04276135)

摘　　要：目的探讨P38丝裂原活化蛋白激酶(P38 mitogen-activated protein kinase,P38 MAPK)、核因子NF-κB(nuclear factor kappa B)和环氧合酶-2(cyclooxygenase-2,COX-2)之间的关系,从而研究P38MAPK和NF-κB、COX-2在1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)制备的帕金森病(PD)小鼠模型的作用机制,以及人参皂甙Rg1(Ginsenoside Rg1,Rg1)对P38MAPK信号通路的影响和对多巴胺神经元的保护作用。方法将小鼠随机分为MPTP模型组、Rg1干预剂组和对照组。观察行为学,采用免疫组织化学和免疫蛋白印迹法观察小鼠黑质酪氨酸羟化酶(TH)、磷酸化P38(p-P38)、NF-κB和COX-2的表达变化;并观察给予人参皂甙Rg1后对上述变化的影响。结果与对照组相比,模型组小鼠出现典型PD症状,TH阳性神经元明显丢失、蛋白水平下降,P38 MAPK信号通路被激活,其磷酸化产物p-P38表达明显增多,NF-κB和COX-2表达也明显增加;经人参皂甙Rg l处理后,上述变化均减轻。结论 P38 MAPK可能通过激活NF-κB、COX-2而诱导帕金森病MPTP模型小鼠黑质多巴胺能神经元(DA)的损伤,P38 MAPK、NF-κB和COX-2在帕金森病的发病过程中可能起重要作用。同时人参皂甙Rg1可能影响P38 MAPK信号通路、NF-κB及COX-2表达而对小鼠多巴胺神经元起到保护作用。【Objective】 To investigate the role of P38 signaling pathway in modulating the expression of NF-κB and cyclooxygenase-2（COX-2） in the substantia nigra（SN） of mice with1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP） induced Parkinson＇s disease（PD）,and explore the possible mechanism of the dopaminergic（DA） neuron death in PD and the effects of Ginsenoside Rg1 on the P38 signaling pathway and DA neurons.【Methods】 C57BL/6N mice were treated with MPTP to produce the subacute PD model,and the behavioral changes were observed.Immunohistochemistry and Western blotting for tyrosine hydroxylase（TH）,NF-κB,COX-2,and phosphorylated P38（p-P38） were used to observe the changes of positive cell number in the midbrain after treatment with ginsenoside Rg1.【Results】 Compared with the control mice,the mice with PD presented with typical symptoms of PD.The number of p-P38,NF-κB,and COX-2 positive cells significantly increased in the SN area（P 0.01）.The number of TH-positive neurons in the PD model group was substantially reduced（P 0.01 vs.control group）.In mice with ginsenoside Rg1 treatment,the number of p-P38,NF-κB,and COX-2 positive cells was reduced obviously as compared with that in the model group（P 0.01）.The number of TH-positive neurons in the SN was decreased by only 23%（P 0.01 vs.control group）.【Conclusions】 P38 signaling pathway may play an important role in modulating NF-κB and COX-2 expression in the SN in the early stage of MPTP-induced subacute PD,and ginsenoside Rg1 may act on the P38 signaling pathway to protect the DA neurons in PD.

关 键 词：帕金森病 磷酸化P38 NF-ΚB 环氧合酶-2 人参皂甙RG1 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]