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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 investigate the behavioral characteristics of levodopa-induced dyskinesia (LID) rat model and to explore objective methods for effectively evaluating the behavioral characteristics of dyskinetic rats. Methods Rats with Parkinson’s disease (PD) damaged by 6-hydroxydopamine were treated with levodopa for 21 days. The behavioral changes were observed and their abnormal involuntary movements (AIM) were scored. The number of tyrosine hydroxylase (TH) immunoreactive cells in substantia nigra (SN) and ventral tegmental area (VTA) was observed by immunohistochemistry. Results AIM gradually developed in PD rats during the treatment of chronic levodopa. The time, manifestations and severity of AIM in each individual began to vary greatly. Compared with non-LID group, the number of TH-positive neurons in the VTA region of the former group was significantly decreased, while that in the SN site was not significantly reduced. NMDA receptor antagonist MK-801 can significantly inhibit the occurrence of rat stereotypes, but has no significant effect on the rotation behavior. After levodopa treatment, the motor function of contralateral forelimbs in lesioned lesions of PD rats was significantly enhanced. After continuous treatment with levodopa, rats gradually developed AIM and progressive development, contralateral forelimb motor function also gradually decreased. CONCLUSION: AIM induced by chronic levodopa in PD rats has similar characteristics with human levodopa-induced dyslipidemia (LID), which provides an effective, economical and practical animal model for the study of LID in humans. At the same time, AIM scoring method and animal forelimb function test is an effective method to evaluate dyskinesia and motor dysfunction in PD rats.