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目的研究多巴胺D1和D2受体以及谷氨酸NMDA受体对△FosB蛋白表达水平的影响,由此探讨它们在左旋多巴诱导的异动症(Levodopa-induced Dyskinesia,LID)发病机制中的作用。方法对单侧黑质纹状体6-羟多巴胺(6-OHDA)损毁致帕金森病(PD)大鼠给予左旋多巴治疗28d制作LID模型,将大鼠分为7组:正常对照组、PD组、LID组、SCH23390治疗组、MK-801治疗组、raclopride治疗组和非LID组,分别观察各组行为学改变并进行异常不自主运动(abnormal involuntary movement,AI M)评分,用免疫组化和免疫印迹方法测定各组△FosB蛋白表达水平。结果多巴胺D1受体阻断剂SCH23390和谷氨酸NMDA受体阻断剂MK-801明显减轻LID大鼠行为学异常,而多巴胺D2受体阻断剂raclopride对异常不自主运动无明显影响;LID大鼠损毁侧纹状体△FosB蛋白表达较PD大鼠和非LID大鼠明显增加;与LID大鼠相比,MK-801和SCH23390均使△FosB蛋白表达显著下降,而raclopride没有这种效应;各组大鼠健侧纹状体△FosB蛋白表达水平没有显著差异。结论多巴胺D1受体和谷氨酸NMDA受体均通过参与调控纹状体△FosB蛋白的表达而影响大鼠LID的发生。
Objective To investigate the effects of dopamine D1 and D2 receptors and glutamate NMDA receptor on the expression of △ FosB protein, and to explore their roles in the pathogenesis of levodopa-induced dyskinesia (LID). Methods LID model was induced in rats with Parkinson’s disease (PD) induced by 6-OHDA damaged by unilateral nigrostriatal system for 28 days. The rats were divided into 7 groups: normal control group, PD group, LID group, SCH23390 treatment group, MK-801 treatment group, raclopride treatment group and non-LID group. The changes of behavior and the abnormal involuntary movement (AI M) The levels of △ FosB protein in each group were determined by Western blotting and Western blotting. Results Dopamine D1 receptor blocker SCH23390 and glutamate NMDA receptor antagonist MK-801 significantly alleviated the behavioral abnormalities in LID rats, whereas dopamine D2 receptor antagonist raclopride had no significant effect on abnormal involuntary movements. LID Compared with LID rats, the expression of △ FosB protein in lesioned side of striatum was significantly increased in rats; both MK-801 and SCH23390 significantly decreased the expression of △ FosB protein, while raclopride had no such effect ; △ FosB protein expression levels in the contralateral striatum of rats in each group were not significantly different. Conclusion Dopamine D1 receptor and glutamate NMDA receptor both affect the occurrence of LID in rats by regulating the expression of △ FosB protein in striatum.