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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。
Aims: To investigate the behavioral changes and the effects of N-methyl-D-aspartate receptor subtype 1 (NR1) in striatum of rats with Parkinson’s disease (PD) after acute and chronic withdrawal of levodopa. Impact. Methods: To establish a rat model of exercise complication. To observe the behavioral changes of rats after administration of levodopa for a long time and after acute withdrawal, and to detect the distribution and phosphorylation of NR1 in striatum by Western blot. Results: (1) After long-term administration of levodopa, PD rats showed a trend of shortening the rotation reaction time and increasing the number of peak rotation cycles, and continued for at least 1 d after withdrawal of drug. After acute treatment and withdrawal of levodopa PD rats did not have this behavioral characteristics. (2) The level of NR1 expression and the phosphorylation of NR1S890, NR1S896 and NR1S897 in PD rat striatum after PDT were significantly higher than those in PD control (P <0.05) after prolonged administration of L-dopa. 1 d. The levels of phosphorylation of NR1S890 and NR1S896 in striatum of PD rats after acute levodopa treatment were higher than those in PD control group (P <0.05), but decreased rapidly after administration of levodopa. CONCLUSION: Long-term treatment with levodopa may lead to complications of exercise and persistent effect after withdrawal. It may be related to the distribution of NR1 in cells and the change of NR1 phosphorylation.