尼莫地平对帕金森病模型小鼠黑质多巴胺神经元的保护作用

Nimodipine protects dopaminergic neurons in the mouse model of Parkinson's disease

目的:研究尼莫地平在1-甲基-4-苯基-1,2,3,6四氢吡啶(MPTP)所致帕金森病(PD)模型小鼠中对黑质多巴胺能神经元的保护作用。方法:雄性健康C57BL/6N小鼠随机分为对照组,腹腔注射生理盐水;模型组,腹腔注射MPTP(25 mg/kg);尼莫地平治疗组,每次注射MPTP前3 h灌胃给予尼莫地平(15 mg/kg)。观察各组小鼠行为学变化,免疫组织化学和免疫蛋白印迹法观察中脑黑质酪氨酸羟化酶(TH)、前列腺素E2(PGE2)和肿瘤坏死因子α(TNF-α)的表达变化。结果:与对照组小鼠比较,MPTP模型组小鼠出现典型的PD症状,中脑黑质TH阳性神经元大量丢失,PGE2和TNF-α阳性细胞显著增多,蛋白水平明显升高;经尼莫地平治疗后,上述症状得到明显改善。结论:在MPTP所致PD小鼠模型中,尼莫地平通过抑制炎症因子PGE2和TNF-α的表达从而对多巴胺能神经元具有一定的保护作用。

Objective： To investigate the protective effect of nimodipine on the dopaminergic neurons in the substania nigra（SN）of MPTP-induced mouse model of Parkinson＇s disease（PD）.Methods： Healthy male C57BL/6N mice were randomly divided into three groups：control group which was treated with saline;model group which was injected with MPTP（25 mg/kg） intraperitoneally;nimodipine group which was treated with nimodipine（15 mg/kg） before injection of MPTP.The behavioral changes of different groups were observed,immunohistochemistry and Western Blot methods were used to investigate the positive cell numbers and the protein expression of prostaglanin E2（PGE2）,TNF-α and tyrosine hydroxylase TH.Results： Compared with control group,the MPTP model group showed typical symptoms of PD with marked loss of TH-positive neurons,the expression level of PGE2 and TNF-α increased significantly.After treating with nimodipine,the above changes were allevated obviously.Conclusion： In the mouse model of Parkinson＇s disease induced by MPTP,nimodipine may play a protective role on the dopaminergic neurons by inhibiting inflammation factors of PGE2 and TNF-α.