同型半胱氨酸对多巴胺能神经元的作用及其机制的研究

Effect and mechanism of homocysteine on dopaminergic neurons

目的 研究同型半胱氨酸 (homocysteine ,Hcy)对帕金森病 (PD)模型动物的多巴胺能神经元的作用及其机制。 方法 40只大鼠被分成 4组 ,通过脑立体定向注射 6 羟多巴胺建立大鼠PD模型 ,2h后同侧脑立体定向注射同型半胱氨酸或生理盐水 ,采用行为学方法 ,免疫组化技术 ,生化方法 ,观察大鼠行为学改变 ,黑质细胞多巴胺能神经元数量、形态改变 ,以及自由基和抗自由基酶的变化。结果 局部注射同型半胱氨酸能明显增加 6 羟基多巴胺所制成的帕金森模型动物的旋转圈数、减少黑质多巴胺能神经元数量以及细胞突起及纤维数逐渐减少 ,并且引起自由基反应增强 ,抗自由基酶减少 ,与对照组存在显著性差异 (P <0 0 5)。结论 Hcy加重PD模型动物的多巴胺能神经元损伤 ,其机制可能与氧化应激反应有关。

Objective To study the effects and mechanism of homocysteine (Hcy) on dopamine neuron in mice model with parkinson’s disease (PD) induced by 6-hydroxydopamine (6-OHDA) in vivo.Methods 40 rats were divided into 4 groups. 6 OHDA or solvent of 6 OHDA was focally administrated to induce PD, 2 hours later Hcy or 0.9% Sodium Chloride were administrated in the ipsolateral substantia nigra. Behavioral testing, immunohistochemical technique biochemistry technique were used to detect the injury of substantia. Results The rotary turns of PD rats induced by 6-OHDA showed significantly increasing after treatment with Hcy compared with the controls ( P <0 05). Also the numbers of TH-stained neurons were decreased, and dendrites were fragmented and truncated. Free radicals were increased and antioxidant enzyme decreased. Conclusions Focal infusion of Hcy into the substantia nigra increased the vulnerability of the dopaminergic neurons to 6-OHDA-induced degeneration, it seemed likely that the endangering effect of Hcy is due to exacerbating oxidative stress.