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目的研究托吡酯对帕金森病大鼠多巴胺能神经元的保护作用。方法将48只雄性Sprague-Dawley大鼠随机分成4组:生理盐水组(A组),6-OHDA组(B组),造模前托吡酯预处理组(C组)和造模后托吡酯处理组(D组),每组各12只;第1～3dA、B、D组分别行生理盐水灌胃,C组用托吡酯稀释后灌胃;第4dB、C、D组分别向右侧纹状体注入6-OHDA,A组注入生理盐水;第5～7dA、B、C组行生理盐水灌胃,D组用托吡酯(剂量同前)稀释后灌胃;分别于造模后第4、28d断头处死,用免疫组织化学方法观察黑质区域内酪氨酸羟化酶(TH)阳性细胞数量,用分光光度计测定纹状体内超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)和丙二醛(MDA)含量。结果与B组损毁侧比较,C、D组损毁侧黑质TH阳性细胞计数明显增多(P<0.01),纹状体内SOD及GSH-Px活性显著增高,MDA含量明显降低,同时C、D组比较差异有显著性(P<0.01)。结论托吡酯对多巴胺能神经元具有保护作用,其保护机制可能与降低脂质过氧化水平及毒性产物的作用和减少自由基的产生有关。
Objective To study the protective effect of topiramate on dopaminergic neurons in Parkinson’s disease rats. Methods 48 male Sprague-Dawley rats were randomly divided into 4 groups: saline group (group A), 6-OHDA group (group B), model topiramate pretreatment group (group C) and model topiramate control group (Group D), 12 rats in each group. Rats in groups 1 to 3dA, B and D were given normal saline respectively. Rats in group C were dosed with topiramate and then intragastrically. Rats in group 4dB, C and D were injected into right striatum The rats in group A were injected with 6-OHDA, group A was injected with saline, groups A, B and C were given normal saline on day 5 to 7, and group D was topically diluted with topiramate at the same time. The animals were sacrificed and the number of tyrosine hydroxylase (TH) positive cells in substantia nigra was observed by immunohistochemical method. The levels of superoxide dismutase (SOD), glutathione peroxidase Enzyme (GSH-PX) and malondialdehyde (MDA) content. Results Compared with the damaged side in group B, the number of TH positive cells in lesioned side of substantia nigra in group C and group D were significantly increased (P <0.01), the activity of SOD and GSH-Px in striatum was significantly increased, while the content of MDA was significantly decreased in group C and D The difference was significant (P <0.01). Conclusion Topiramate has a protective effect on dopaminergic neurons. Its protective mechanism may be related to the reduction of lipid peroxidation, the effect of toxic products and the reduction of free radicals.