左旋多巴急性与长期作用后撤药对帕金森病大鼠行为学及N-甲基-D-天冬氨酸受体亚型1的影响  

Effects of Withdrawal After Acute and Chronic L-dopa Treatment on Behaviour and 1 Type N-methyl-D-aspartate Receptor Property of Parkinson’s Disease Rats

作　　者：孔敏[1] 巴茂文[2] 刘振国[1] 

机构地区：[1]上海交通大学医学院附属新华医院神经内科,200092 [2]山东省烟台市毓璜顶医院神经内科,264000

出　　处：《中国临床神经科学》2009年第3期256-260,共5页Chinese Journal of Clinical Neurosciences

基　　金：上海市浦江人才计划(PJ[2007]00346);上海市科委上海-飞利浦研究与发展基金合作基金(07SP07005)

摘　　要：目的:探讨左旋多巴急性与长期作用后撤药对帕金森病(PD)大鼠行为学及对纹状体区N-甲基-D-天冬氨酸受体亚型1(NR1)特性的影响。方法:建立运动并发症大鼠模型。观察左旋多巴长期及急性治疗后撤药1 d大鼠的行为学变化,用Western blot检测纹状体区NR1在细胞的分布及磷酸化的水平。结果:①左旋多巴长期作用后的PD大鼠呈现旋转反应时间逐渐缩短而剂峰旋转圈数增加的趋势,且撤药后仍可持续至少1 d;左旋多巴急性处理及撤药后的PD大鼠则未无此行为学特点。②左旋多巴长期作用后的PD大鼠纹状体胞膜NR1表达水平以及NR1S890、NR1S896和NR1S897的磷酸化水平均明显高于PD对照(P<0.05),撤药后其表达量仍可持续1 d;左旋多巴急性作用后的PD大鼠纹状体胞膜NR1S890和NR1S896磷酸化水平均高于PD对照组(P<0.05),但撤药后很快降低。结论:左旋多巴长期治疗带来的运动并发症及其撤药后持续效应可能与NR1在细胞的分布及NR1磷酸化水平改变有关。Aim： To explore the effects of withdrawal after acute and chronic L-dopa treatment on Parkinson＇ s disease（PD） rat behaviour and NR1 property. Methods： Rat models of motor complications in PD were made according to the method of Ba et al, and the rats behavioural changes were observed at withdrawal for 1 day after chronic or acute L-dopa treatment. The distribution of NR1 and levels of phosphorylated NR1 （NR1 S890, NR1 S896 and NR1S897） were detected by using Western blot. Results： （1）The PD rats with chronic treated by L-dopa displayed a shortened and increased tendency in rotational duration and peak rotation, respectively, which was kept for 1 day at least after withdrawal. However, the same behavioural characterastics were not appeared in the rats with acute treated by L-dopa and withdrawal. （2） Levels of NR1 and phosphorylated NRIS890, NRlS896 and NR1S897 in the striatal cellular membranes were distinctly increased in the PD rats with chronic treated by L-dopa compared with the PD rats taken as control, which also be kept for 1 day at least after withdrawal. The levels of indexes mentioned above were increased mildly in the rats with acute treated by L-dopa, but was quickly down-regulated after withdrawal. Conclusion： The motor complications and persistence after withdrawal in the PD rats with chronic treated by L-dopa may be contributed to the distribution and phosphorylation of NR1.

关 键 词：左旋多巴 旋转 N-甲基-D-天冬氨酸受体亚型1 磷酸化 撤药 

分 类 号：R742.5[医药卫生—神经病学与精神病学]