磷酸化P38 MAPK对帕金森病MPTP模型小鼠黑质caspase-3表达的影响

Effect of phosphorylated-P38 MAPK on caspase-3 expression in substantia nigra of the MPTP mouse model of Parkinson's disease

目的研究磷酸化P38 MAPK在1-甲基-4-苯基-1,2,3,6四氢吡啶(MPTP)所致帕金森病(PD)模型小鼠中对黑质半胱氨酸蛋白酶-3(caspase-3)的调控作用。方法将小鼠随机分为MPTP模型组,腹腔注射MPTP(30mg/kg,生理盐水溶);抑制剂组,在注射MPTP前1h腹腔注射SB203580(10mg/kg,溶于5mg/mLDMSO)。均1次/d,连续5d;对照组,注射与模型组和抑制剂组等量生理盐水和DMSO。观察行为学、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)、caspase-3和磷酸化P38 MAPK(p-P38MAPK)的表达。结果与对照组相比,模型小鼠出现典型的PD症状,TH阳性神经元和蛋白水平分别下降约60%和65%(P<0.01),p-P38 MAPK、caspase-3阳性细胞及蛋白水平显著增加(P<0.01);经P38 MAPK抑制剂SB203580处理后,上述变化均显著减轻(P<0.01)。结论磷酸化P38 MAPK在MPTP诱导的PD小鼠黑质caspase-3表达中可能有重要调控作用,SB203580对PD小鼠具有一定的神经保护作用。

Objective To investegate the effect of phosphorylated-P38 MAPK（ mitogen-activated protein kinase） on the expression of caspase-3 in the substania nigra（SN） of MPTP-induced mouse model of（PD）. Methods Mice were randomly divided into MPTP model group, which were treated with MPTP and inhibitor group. Once a day for 5 days; control group was treated with saline and DMSO as much as the model group received per day for 5 days. The behavioral were observed, immunohistochemistry and Western blot for TH, caspase-3 and phosphorylation of P38 MAPK were used to observe the change of positive cell number and the expression level in the SN of midbrain. Results Compared with the mice in control group, the model group showed typical symtoms of PD with decreased numbers of TH-positive neurons and the protein level of TH in SN of the midbrain by about 60% and 65% respectively（P 〈0.01 ） , the numbers of caspase-3 and phosphorytation of P38 MAPK immunoreactive cells and their protein level in the SN of the midbrain increased markedly （P 〈 0. 01 ）. After giving SB203580, the above changes were reduced obviously （P 〈0.01 ）. Conclusion In the mouse model of subaeute Parkinson＇s disease induced by MPTP, phosphorylated-P38 MAPK regulated easpase-3 in the SN of midbrain, the specific P38 MAPK inhibitor SB203580 is neurologically oprotective to the mouse model.