左旋多巴诱发异动症大鼠模型的制作及其行为学评估  

Preparation and assessment of the behavior of the rat model of levodopa-induced dyskinesias

作　　者：徐岩[1] 孙圣刚[1] 曹学兵[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经内科,武汉430022

出　　处：《中华物理医学与康复杂志》2005年第11期649-652,共4页Chinese Journal of Physical Medicine and Rehabilitation

摘　　要：目的探讨左旋多巴诱发异动症(LID)大鼠模型的行为学特点,以及探寻有效评估异动症大鼠行为学特点的客观方法。方法对6-羟多巴胺损毁致帕金森病(PD)大鼠给予左旋多巴治疗21d,观察其行为学改变,并对其异常不自主运动(AIM)进行评分。采用免疫组织化学方法观察大鼠黑质(SN)及腹侧被盖部(VTA)区域酪氨酸羟化酶(TH)免疫阳性细胞的数量。结果PD大鼠在慢性左旋多巴治疗过程中,会逐渐出现AIM,各个体间AIM开始出现的时间、表现形式及严重程度等差异较大。LID组与非LID组比较,前者VTA部位TH阳性神经元数量明显减少,而SN部位则减少不显著。NMDA受体拮抗剂MK-801能明显抑制大鼠刻板动作的发生,而对其旋转行为无明显影响。经左旋多巴治疗后,PD大鼠损毁灶对侧前肢运动功能明显增强,且经左旋多巴持续治疗后,大鼠逐渐出现AIM并呈进行性发展,对侧前肢运动功能亦逐渐减退。结论由慢性左旋多巴治疗PD大鼠诱导其产生的AIM与人类左旋多巴诱导的异动症(LID)具有相似的特点,为人类LID的研究提供了有效、经济、实用的动物模型;同时发现AIM评分方法及动物前肢功能实验是评估PD大鼠异动症及运动功能减退的有效方法。Objective To study the behavioral characteristics of a rat model of the levodopa-induced dyskinesia （LID） and the related factors, and to define clinically the relevant methods for assessing akinesia and dyskinesia in LID rats. Methods Unilaterally lesioned rat model of Parkinson＇s disease using 6-hydroxydopamine were treated by levodopa and benserazide once daily for 3 weeks, on the 21st day the acute systemic administration of MK801 was performed 15 min prior to levodopa treatment to observe the behavior （abnormal involuntary movement, rotation behavior and forelimb stepping） and to estimate the quality of AIM by using the rat AIM rating scale. Immunohistochemical technique was used to measure the number of TH-positive neurons in the substantia nigra （SN） and ventral tegmental area （VTA） , which was then correlated to the AIM scores. Results Pulsatile treatment with a subthreshold dose of levodopa gradually induced abnormal involuntary movement （AIM） , including stereotypy （limb dyskinesia, axial dystonia and masticatory dyskinesia） towards the side contralateral to the dopamine-denervated striarum and increased rotational behavior. The onset of AIM and motor pattern of each subtype was highly stereotypic across individual rats, and the proportion of each subtype was not consistent among individual rats. The number of TH-positive neurons in the VTA, but not in the SN, was significantly decreased in the LID rats compared with the non-LID rats. MK-801 prevented stereotypy but not rotational behavior. Contralateral forepaw performance was significantly improved after levodopa treatment, but gradually reduced with more and more severe AIM following repeated levodopa therapy. Conclusion Levodopa-induced rat AIM model of PD demonstrated similar properties with the levodopa-induced dyskinesia （LID） in PD patients, and provided an effective tool for LID study. AIM rating and forelimb stepping test are useful for evaluating the dyskinesia and akinesia of PD rats.

关 键 词：左旋多巴 异动症 异常不自主运动 大鼠 

分 类 号：R-332[医药卫生]