左旋多巴诱发异动症大鼠模型的制作及其行为学研究  

Establishment of a rat model of levodopa induced dyskinesia and its behavior characteristics

作　　者：孙慧勤[1] 陈先文[1] 李芳[1] 许奇[2] 王烈成[2] 李光武[3] 

机构地区：[1]安徽医科大学第一附属医院神经内科,合肥230032 [2]安徽医科大学生理学教研室,合肥230032 [3]安徽医科大学解剖学教研室,合肥230032

出　　处：《安徽医科大学学报》2009年第3期355-358,共4页Acta Universitatis Medicinalis Anhui

基　　金：安徽省科学自然基金(编号:01043401)

摘　　要：目的探讨左旋多巴(L-dopa)诱发帕金森病(PD)大鼠异动症模型的建立,以及多巴胺受体激动剂与拮抗剂对异动症大鼠不自主运动的影响。方法6-羟多巴胺(6-hydroxydopamine,6-OHDA)立体定向注射制备偏侧PD大鼠模型并给予L-dopa+苄丝肼治疗21d,对其异常不自主运动(AIM)进行录像并评分,观察肢体运动功能及旋转行为改变情况。对出现异动症的大鼠给予多巴胺受体激动剂和拮抗剂并观察其行为学改变。结果PD大鼠在接受L-dopa慢性治疗后出现不自主运动,第3天评分:(31.13±0.32)分,肢体运动功能在接受治疗过程中同时改善。D2受体激动剂可诱发大鼠不自主运动(48.24±1.27)分,D2受体拮抗剂可减轻L-dopa诱发的大鼠不自主运动(41.93±2.27)分,但同时拮抗L-dopa运动功能改善效应。结论慢性脉冲式L-do-pa治疗PD大鼠可以诱发大鼠AIM,与人类L-dopa诱导的异动症(LID)具有相似的特点,可作为研究异动症的动物模型。Objective To establish a rat Parkinson＇s disease （PD） model of the levodopa-induced dyskinesia（LID） and examine the behavioral characteristics. Methods Hemi-parkinsomism rat model was made by 6-OHDA micro-injection stereotaxically, then treated with chronic intermittent L-dopa ＋ benseride injection for 21 days. The abnor- mal involuntary movement behavior was recorded by video and the abnormal involuntary movement （AIM） scores were estimated using the rat AIM rating scale. The limb movement function and the rotation behavior were also examined. The behavior response of LID rats to D2 dopamine receptor agonist and antagonist were checked to identify the pharmaceutical characteristics. Results Treatment with levodopa in PD rats gradually induced abnormal involuntary movement （AIM） , the AIM scores of this group were significantly higer than those of the normal control group and the Parkinson＇s disease control group. Contralateral forepaw performance was significantly improved and the rotational behavior decreased after levodopa treatment. D2 receptor agonist could induce AIM, while D2 receptor antagonist could alleviate AIM but counteract the forepaw performance in LID rats, indicating this model was similar in response to pharmaceutical stimulation to human PD patients. Conclusion Chronic treatment with levodopa intermittently can induce AIM in hemi-parkinsomism rats. This rats show similar behavioral and pharmaceutical characterization to PD patients with levedopa-induced dyskinesia and can be used as a LID model.

关 键 词：左旋多巴 帕金森病 疾病模型 动物 

分 类 号：R745.7[医药卫生—神经病学与精神病学] R971.5[医药卫生—临床医学]