P38通路对帕金森病小鼠模型黑质环氧合酶-2、半胱氨酸蛋白酶-3表达的影响  

P38MAPK pathway regulates COX-2 and caspase-3 expression in a mouse model of Parkinson disease

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

机构地区：[1]华北煤炭医学院解剖学教研室,河北唐山063000

出　　处：《南方医科大学学报》2009年第10期2010-2013,2017,共5页Journal of Southern Medical University

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);唐山市科学技术研究与发展计划(09130202A-3-19)

摘　　要：目的研究P38MAPK通路在1-甲基-4-苯基-1,2,3,6四氢吡啶(MPTP)所致亚急性帕金森病(PD)小鼠模型中对黑质环氧合酶-2(COX-2)、半胱氨酸蛋白酶-3(caspase-3)表达调控作用。方法采用MPTP制备PD小鼠模型,观察行为学、免疫组化和免疫蛋白印记法观察小鼠黑质酪氨酸羟化酶(TH)、COX-2、caspase-3和磷酸化P38MAPK(p-P38MAPK)的变化,及给予P38MAPK抑制剂SB203580后对上述变化的影响。结果模型7d组小鼠出现典型的PD样症状,黑质区TH阳性神经元和蛋白水平分别下降约65%和75%(P<0.01);模型3d组小鼠黑质区COX-2、p-P38MAPK、caspase-3阳性细胞数及蛋白水平显著增加,TH阳性神经元明显丢失;经P38MAPK抑制剂SB203580处理后,上述变化均显著减轻(P<0.01)。结论在MPTP所致亚急性小鼠PD模型中,P38MAPK通路对黑质区炎症与凋亡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） on the expression of COX-2 and caspase-3 in the substania nigra （SN） of mice with MPTP-induced Parkinson disease （PD）. Methods C57BL/CN mice were treated with MPTP to prepare a subacute PD model, and their behavioral changes following the treatment were observed. Immtmohistochemistry and Western blotting were performed to detect the expression of tyrosine hydroxylase （TH）, COX-2 and phosphorylation of P38MAPK in the SN and their changes following treatment with SB203580, a specific inhibitor of P38MAPK. Results The 7-day model group showed typical symptoms of PD with decrements of TH-positive neurons and TH protein level in the SN of the midbrain by about 65% and 75%, respectively （P〈0.01）. In the 3-day model group, the COX-2-, caspase-3- and phosphorylated P38MAPK-immunoreactive cells and their protein levels in the SN increased markedly with obvious loss of TH-positive neurons. Administration of SB203580 obviously lessened the above changes （P〈0.01）. Conclusion P38MAPK regulates the inflammation and apoptosis in the SN of the mouse model of subacute PD, and SB203580 may provide some neuroprotective effect.

关 键 词：帕金森病 炎症 凋亡 环氧合酶-2 半胱氨酸蛋白酶-3 P38MAPK 磷酸化P38MAPK 

分 类 号：R742.5[医药卫生—神经病学与精神病学]