P38丝裂原活化蛋白激酶对帕金森病模型小鼠黑质诱导型一氧化氮合酶和前列腺素E2表达的影响  

P38MAPK regulates iNOS and PGE2 expression in substantia nigra in mouse model of Parkinson＇s disease

作　　者：魏子峰[1] 张作凤[1] 王永生[1] 王茜[1] 张宇新[1] 

机构地区：[1]华北煤炭医学院解剖学教研室,唐山063000

出　　处：《解剖学杂志》2010年第1期77-81,共5页Chinese Journal of Anatomy

基　　金：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）

摘　　要：目的：研究P38丝裂原活化蛋白激酶（P38MAPK）在1-甲基-4-苯基-1，2，3，6四氢吡啶（MPTP）所致帕金森病（PD）模型小鼠中对黑质诱导型一氧化氮合酶（iNOS）和前列腺素E2（PGE2）的调控作用。方法：将小鼠随机分为MPTP模型组，腹腔注射MPTP；抑制剂组，每次注射MPTP前1h腹腔注射P38MAPK特异性抑制剂SB203580；对照组，注射与模型组和抑制剂组等量生理盐水和DMSO。行为学观察，采用免疫组织化学和免疫蛋白印迹法观察黑质酪氨酸羟化酶（TH）、iNOS、PGE2和磷酸化P38MAPK（p—P38MAPK）的表达。结果：模型组小鼠出现PD典型的行为学症状，TH阳性细胞和蛋白水平下降61%～65％，p-P38MAPK、iNOS和PGE2阳性细胞及蛋白水平显著增加；经SB203580处理后，上述变化均明显减轻。结论：P38MAPK对PD模型小鼠黑质iNOS和PGE2表达可能有重要调控作用，SB203580对PD小鼠具有一定神经保护作用。Objective： To investigate the effect of P38 mitogen-activated protein kinase （P38MAPK） pathway on the expression of inducible nitric oxide synthase （iNOS） and prostaglandin E2 （PGE2） in the substantia nigra （SN） of MPTP-induced mouse model of Parkinson＇s disease （PD）. Methods： Healthy male C57BL/6N mice were randomly divided into 3 groups： MPTP model group treated with MPTP; inhibitor group treated with SB203580 1 hour before injection of MPTP; control group treated with saline and DMSO as much as the model group. The behavior was observed. By immunohistochemistry and Western blot, TH, iNOS, PGE2 and phosphorylation of P38MAPK were detected to observe the changes of positive cell numbers and the expression level in the SN of midbrairu Results： The model group showed typical symptoms of PD with de- creased number of tyrosine hydroxylase （TH）-positive neurons and a decrease in the protein level of TH in SN of the midbrain by 610/4- 65 %. The number of iNOS, PGE2 and phosphorylated P38 MAPK （p-P38MAPK） immunoreactive cells and their protein level in the SN of the midbrain increased markedly. After giving SB203580, the above changes were alleated ob- viously. Conclusion： In the mouse model of subacute Parkinson＇s disease, P38MAPK pathway regulates the expression of iNOS and PGE2 in the SN of midbrain, indicating that SB203580 is neuroprotective to the mouse model.

关 键 词：帕金森病 诱导型一氧化氮合酶 P38丝裂原活化蛋白激酶 酪氨酸羟化酶 前列腺素E2 

分 类 号：R364.12[医药卫生—病理学] R743.31[医药卫生—基础医学]