CAJ | 학술논문

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SB 203580;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SB 203580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,SB 203580对PD小鼠具有一定神经保护作用.
목적:연구P38사렬원활화단백격매(P38MAPK)재1-갑기-4-분기-1, 2, 3, 6사경필정(MPTP)소치파금삼병(PD)모형소서중대흑질유도형일양화담합매(iNOS)화전렬선소E2(PGE2)적조공작용.방법:장소서수궤분위 MPTP모형조,복강주사MPTP;억제제조,매차주사MPTP전1h복강주사P38MAPK특이성억제제SB 203580;대조조,주사여모형조화억제제조등량생리염수화DMSO.행위학관찰,채용면역조직화학화면역단백인적법관찰흑질락안산간화매(TH)、 iNOS、 PGE2화린산화P38MAPK (p-P38MAPK)적표체.결과:모형조소서출현PD전형적행위학증상,TH양성세포화단백수평하강61%～65%, p-P38MAPK、 iNOS화PGE2양성세포급단백수평현저증가;경SB 203580처리후,상술변화균명현감경.결론: P38MAPK대PD모형소서흑질iNOS화PGE2표체가능유중요조공작용,SB 203580대PD소서구유일정신경보호작용.
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 midbrain. Results: The model group showed typical symptoms of PD with decreased number of tyrosine hydroxylase (TH)-positive neurons and a decrease in the protein level of TH in SN of the midbrain by 61%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 obviously. 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.