【摘要】 目的观察尼莫地平对帕金森病模型鼠多巴胺能神经元中Bcl-2、P53蛋白表达的影响,从而探索尼莫地平对黑质多巴胺能神经元的保护作用。方法建立大鼠PD模型,分组、分阶段用尼莫地平进行干预,第一阶段为尼莫地平对PD模型的预先干预,第二阶段为成功PD模型的药物治疗(尼莫地平、左旋多巴),其后均由阿朴吗啡(Apomorphine)诱导旋转行为,最后予大鼠黑质细胞进行HE、TH、Bcl-2、P53染色。结果第一阶段:尼莫地平PD模型组(Ⅰ组)和PD模型组(Ⅱ组),成功模型右侧黑质Bcl-2蛋白表达阳性细胞百分比较假手术组(Ⅲ组)和正常对照组(Ⅳ组)低(P<0.05),而P53蛋白表达阳性细胞百分比较Ⅲ组和Ⅳ组高(P<0.05);Ⅰ组右侧黑质Bcl-2蛋白表达阳性细胞百分比高于Ⅱ组(P<0.05),而P53蛋白表达阳性细胞百分比低于Ⅱ组(P<0.05);第二阶段:尼莫地平组、左旋多巴组或二者联用干预组与生理盐水组间右侧黑质Bcl-2、P53蛋白表达阳性细胞百分比无统计学差异(P>0.05)。结论尼莫地平在蛋白合成水平促进了Bcl-2表达、抑制了P53表达,减缓了多巴胺能神经元的凋亡。更多还原

【Abstract】 Objective This study examined the effect of Nimodipine on the expression of Bcl-2 and P53 protein in dopaminergic neurons of rats with Parkinson’s disease (PD) in order to explore neuroprotective effects of Nimodipine. Methods Rat PD model was prepared by 6-OHDA injection, and rotational behaviors were induced by apomorphine (PD model group, n=25). Another 25 rats were pretreated with Nimodipine (10 mg/kg/d) 2 weeks prior to 6-OHDA injection (Nimodipine-pretreated group) and rotational behaviors were induced 15 days later. Another 40 PD!rats were randomly treated with Nimodipine (10 mg/kg/d), Levodopa (15 mg/kg/d), Nimodipine + Levodopa or normal saline and then rotational behaviors were induced by apomorphine. Expression of Bcl-2 and P53 protein in dopaminergic neurons was detected by HE, TH, Bcl-2 and P53 staining. Results The expression of Bcl-2 protein in the right pars compacta of substantia nigra (SNc) of the Nimodipine-pretreat and the PD model group was significantly lower, but P53 protein expression was significantly higher than that of the sham-operated and the normal control groups (P<0.05). The Nimodipine-pretreated group showed higher Bcl-2 protein expression and lower P53 protein expression in the right SNc than the PD model group. There were no significant differences in the expression of Bcl-2 protein and P53 protein among the Nimodipine, the Levodopa, the Nimodipine + Levodopa, and the normal saline groups. Conclusions Nimodipine can up-regulate Bcl-2 protein expression and down-regulate P53 protein expression and thus attenuates the apoptosis of dopaminergic neurons.更多还原