异动症大鼠模型基底节DARPP-32蛋白磷酸化状态的变化

目的观察左旋多巴诱发异动症(LID)大鼠模型行为学特点及DARPP-32蛋白的磷酸化状态的变化,探讨LID的发生机制。方法复制成功的帕金森病(Parkinson disease PD)大鼠应用左旋多巴治疗28d诱发LID大鼠模型,进行异常不自主运动(abnormalinvol untary movement,AIM)评分,并采用免疫印迹技术检测LID大鼠纹状体内DARPP-32蛋白Thr-34位点磷酸化水平。结果LID大鼠模型复制成功后出现了与人类LID相似的对侧上肢、躯干和口面部异常不自主运动(AIM),并随左旋多巴治疗时间的延长而加重。LID组大鼠纹状体内Thr-34位点磷酸化的DARPP-32水平较对照组与左旋多巴治疗组明显增高,又以重度LID组大鼠更为显著,差异有显著性意义(P<0.01)。结论慢性间断性给PD大鼠左旋多巴能复制出LID大鼠模型,其纹状体区DARPP-32蛋白的磷酸化状态发生了改变,与LID的发生可能有关。

Changes of Dopamine and CAMP-regulated Phosphoprotein (DARPP-32) phosphorylation expression in the basal ganglia of levodopa-induced dyskinesia rat

Objective] To study the character of movement and change of Dopamine and CAMP-regulated Phosphoprotein(DARPP-32) phosphorylation expression in order to explore the mechanism in rats with Levodopa-induced dyskinesias. Methods] PD rats received twice daily Levodopa celiac (10 mg/kg) injections for 28 days to get the LID rats. The normal rats received same course and dosage of Levodopa as a control group. Phospho-Thr-34 DARPP-32 level were measured by immunoblotting. Results] Pulsatile treatment with Levodopa induced contralateral forelimb, trunk and orofacial abnormal involuntary movement(AIM) in PD rats , similar to LID in PD patients. Compared to control and Levodopa treatment rats(P <0.01), the levels of phospho-Thr-34 DARPP-32 increased significantly in LID groups, especially in severe LID group. Conclusion] LID model in rats could be established by intermittent treatment with Levodopa to PD rats. Phospho-Thr-34 DARPP-32 level was increased in LID rats, which contribute to the over-activation in direct-pathway.