P38信号通路调控帕金森病小鼠黑质NF-κB和iNOS的表达  

P38 MAPK signaling pathway regulates nuclear factor-κB and inducible nitric oxide synthase expressions in the substantia nigra in a mouse model of Parkinson's disease

作　　者：王茜[1] 张辉[2] 刘名[3] 张作凤[1] 魏子峰[1] 孙娜[4] 毛彤瑶 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病科,河北唐山063000 [3]唐山市协和医院骨科,河北唐山063000 [4]河北联合大学基础医学院生理学系,河北唐山063000

出　　处：《南方医科大学学报》2014年第8期1176-1180,共5页Journal of Southern Medical University

基　　金：唐山市科学技术研究与发展计划指令项目(13130267z);河北联合大学科学研究基金(Z201236);河北联合大学2013年大学生创新性实验计划(X2013034);2013年河北省大学生创新创业训练计划项目(201310081023)

摘　　要：目的探讨P38丝裂原活化蛋白激酶(P38 MAPK)信号通路与核因子NF-κB、一氧化氮合酶(inducible nitricoxide,iNOS)之间的关系,通过给予P38 MAPK特异性抑制剂SB203580,研究P38 MAPK信号通路在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。方法将小鼠随机分为模型组、干预组和对照组。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酪氨酸羟化酶(TH)、磷酸化P38(p-P38)、NF-κB和iNOS的表达变化;以及给予SB203580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iNOS表达也明显增加;经SB203580干预处理后,上述变化均减轻。结论 P38 MAPK信号通路可能参与激活NF-κB、iNOS而诱导PD模型小鼠黑质多巴胺能神经元的损伤,采用SB203580抑制P38 MAPK信号通路可对PD模型小鼠多巴胺神经元起到保护作用。Objective To investigate the role of P38 mitogen-activated protein kinase （P38 MAPK） signaling pathway in regulating the expression of nuclear factor-κB （NF-κB） and inducible nitric oxide synthase （iNOS） in the substantia nigra （SN） of a mouse model of Parkinson＇s disease （PD）. Methods C57BL/6N mice were treated with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine （MPTP） to establish an subacute PD model and the behavioral changes of the mice were observed. Immunohistochemistry and Western blotting were employed to detect the expressions of tyrosine hydroxylase （TH）, NF-κB, iNOS and phosphorylated P38 （p-P38） in the midbrain before and after treatment with SB203580. Results Compared with the control mice, the PD mouse models presented with typical symptoms of PD and showed significantly increased number of p-P38-, NF-κB-, and iNOS-positive cells in the SN area （P〈0.01） with significantly reduced number of TH-positive neurons （P〈 0.01）. After SB203580 treatment, the number of p-P38-, NF-κB, and iNOS-positive cells was reduced obviously （P〈0.01） and the number of TH-positive neurons in the SN increased significantly in the PD model mice （P〈0.01）. Conclusion P38 MAPK signaling pathway may play an important role in modulating NF-κB and iNOS expression in the SN in the early stage of MPTP-induced subacute PD, and S0203580 can inhibit P38 signaling pathway to protect the DA neurons in PD model mice.

关 键 词：帕金森病 磷酸化P38 NF-ΚB 一氧化氮合酶 SB203580 

分 类 号：R742.5[医药卫生—神经病学与精神病学]