SB203580对帕金森病模型小鼠多巴胺神经元的保护作用

SB203580 protects dopaminegic neurons in the mouse model of Parkinson's disease

目的研究SB203580在1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)所致帕金森病(PD)小鼠模型中抑制P38MAPK(mitogen-activated protein kinase)通路对多巴胺(DA)能神经元保护作用。方法健康雄性C57BL/6N小鼠45只随机分为3组: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/ml DMSO),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记法观察黑质酪氨酸羟化酶(TH)、caspase-3和磷酸化P38MAPK(p-P38MAPK)表达,及做TUNEL标记检测。结果模型组小鼠出现PD典型行为学表现,TH阳性神经元和蛋白水平分别下降约60%和65%(P<0.05),p-P38MAPK和caspase-3阳性细胞大量表达,蛋白水平显著升高,TUNEL标记的阳性细胞大量出现;抑制剂组小鼠上述变化明显减轻(P<0.05)。结论在MPTP所致PD模型小鼠中,SB203580通过抑制p38MAPK通路减少凋亡蛋白caspase-3表达,从而发挥神经保护作用。

Objective To investegate the proteetive effect of SB203580 on dopaminegie neurons apoptosis in the subatania nigra（SN） of MPTP-indueed mouse model of Parkinson＇s disease （PD）, through inhibition of P38MAPK（ mitogenactivated protein kinase）. Methods Healthy male C57BL/6N mice were randomly divided into 3 groups：model group, which were treated with MPTP（ 30mg/kg, dissolved in saline, intraperitoneal injection） ; inhibitor group, which were treated with SB203580 （ 10mg/kg, dissolved in 5mg/ml DMSO, intraperitoneal injection） 1 h before injection of MPTP, once a day for 5 days ; control group were treated with saline and DMSO as much as the model group received. The behavioral changes were observed. Mice were sacrificed for immunohistoehemieal staining,western blot and TUNEL studies. Results The model group showed typical symtoms of PD with the decreased numbers of TH-positive neurons and the protein level of TH in SN of the midbrain by about 60% and 65% respectively（P 〈0.05）. p-P38, easpase-3 and TUNEL positive cells increased markedly,with decreased protein level. In inhibitor group, the above changes were reduced obviously （ P 〈 0. 05 ）. Concinlion In the mouse model of Parkinsen＇s disease induced by MPTP, SB203580 may play a neural protection effect by inhibiting the easpase-3 expression.