摘要
目的:研究左旋多巴(L-dopa)对黑质细胞的神经毒性作用,探讨合理应用L-dopa治疗帕金森病(Parkinson disease,PD)的方法。方法:通过6-OHDA脑立体定向注射术建立大鼠PD模型,采用行为学、细胞凋亡(TUNEL观测法)、原位杂交的方法观察L-dopa小、中、大三种不同剂量[10 mg/ (kg·d)、50 mg/(kg·d)、100 mg/(kg·d)]在1、3、5、7天不同的作用时间对PD大鼠黑质细胞的毒性作用,以及治疗7天后各项指标的变化。结果:PD大鼠旋转行为、细胞凋亡数、Bcl-2 mRNA随着L-do- pa治疗的时间的延长和剂量的增加而增加,P53 mRNA在1天迅速达高峰,此后逐渐下降。除小剂量组外,中、大剂量L-dopa组各项指标均高于对照组(P＜0．05),停止治疗7天后,L-dopa治疗各组指标均得到改善。结论:L-dopa能加速PD大鼠黑质细胞凋亡,这种作用受到Bcl-2 mRNA、P53 mRNA调控,小剂量、间隔使用L-dopa能有效减少其神经毒性作用。
Objective：To evaluate the neuronal toxicical effects induced by L-dihydroxy-phenylanine （L-dopa） and to explore the method by which Parkinson disease（PD） can be treated reasonablely with L- dopa. Methods： The rat models of PD were made by injecting 6-OHDA stereotaxically to right side of the mesencephic ventral tegmental araea（VTA） and substantia nigra pars compacta（SNc）. The PD rats were treated intraperitoheally with different dosages E10 mg/（kg · d）. 50 mg/（kg · d）. 100 mg/（kg · d） ] of L-dopa and different durations（1 d,3 d,5 d,7 d） after L-dopa injection. At the same time , the injury of substantia nigral was observed, by treating PD rats with L-dopa for 7 days rotational behaviour induced by apomorphine, TUNEL, in situ H-ybridization techniques to detect the injury of substantia nigra by different dosages of L-dopa and durations after L-dopa injection . Results： The rotational behaviour , substantia nigral apoptosis , Bcl-2 Mrna increased with increase of the dosages and durations of L-dopa. P53 Mrna got to peak value promptly at 1 d and then decreased gradually. Except the PD group treated with l.-dopa doses of 10 mg/（kg, d） , each index of other PD groups was more than that of the control group（P〈0.05）. Seven days after L-dopa stopped in each group , the above indexes were improved. Conclusions： If L-dopa is properly used, the toxical action of L-dopa can be reduced.
出处
《临床神经电生理学杂志》
2007年第2期67-70,73,共5页
Journal of Clinical Electroneurophysiology
基金
国家自然科学基金(编号:3040051621)
湖北省卫生厅科研基金(编号:3-110)支助
