中文摘要：

目的观察不同剂量左旋多巴（LD）对帕金森病（PD）大鼠神经行为学的影响。方法采用6-羟基多巴胺（6-OHDA）脑立体定向注射术建立大鼠PD模型,并将成功PD模型随机分成2组,分别每日腹腔注射20 mg/kg和50 mg/kg LD,共28 d。在不同时间点（3、7、10、14、17、21、242、8 d）,观察PD模型大鼠的神经行为学（大鼠对侧旋转圈数、大鼠异常不自主运动评分、旋转启动时间、旋转持续时间、药效期、药效期平均旋转圈数和剂峰旋转圈数）的变化。结果 PD大鼠注射不同剂量LD后均逐渐出现不自主动作（AIM）表现,且随着LD用药时间的延长,阿扑吗啡（APO）诱导的对侧旋转圈数、药效期平均旋转圈数及剂峰旋转圈数均呈不断增加趋势,且20 mg/kg剂量组的各指标变化值在不同时间点均高于50 mg/kg剂量组,其中对侧旋转圈数在14 d和21 d时差异有统计学意义（P〈0.05）;AIM评分、旋转持续时间及药效期50 mg/kg剂量组均有不断增加的趋势,20 mg/kg剂量组则先减少后增加,且20 mg/kg剂量组的变化值均低于50 mg/kg剂量组,其中旋转持续时间在7、14、172、4 d和28 d时差异有统计学意义（P〈0.05或P〈0.01）,药效期在71、4 d和28 d时差异有统计学意义（P〈0.01）,旋转启动时间20 mg/kg剂量组有先增加后减少趋势,50 mg/kg剂量组则有先减少后增加趋势;50 mg/kg剂量组LD各指标的变化趋势明显且稳定。结论 20 mg/kg和50 mg/kg剂量LD长期治疗对PD大鼠黑质细胞均有神经毒性作用,以50 mg/kg剂量LD的神经毒性作用更为明显。

英文摘要：

Objective To observe the neuroethology of rats with Parkinson＇s disease（PD） treated by different doses of levodopa.Methods The PD rat models were established through stereotoxic injection of 6-hydroxydopamine.The successful models of PD were randomized into two groups,which were then treated intraperitoneally with 20mg/kg and 50mg/kg doses of levodopa for 28 days.Then at different time points（i.e.,3d,7d,10d,14d,17d,21d,24d and 28d）,we observed the behavioral changes of PD model rats,including the circle count induced by apomorphine（APO）,scoring of abnormal involuntary movement（AIM）,start-up time of rotation,duration of rotation,time of pharmacodynamic action,average circle count in pharmacological action,and circle count of peak rotation.Results After administration of different doses of levodopa,all the rats with PD gradually displayed the abnormal involuntary movement,and as the time of levodopa administration was prolonged,the circle count induced by APO,the average circle count in pharmacological action and the circle count of peak rotation all gradually increased.The score of each index in 20mg/kg dose group was higher than that in 50mg/kg dose group;the circle count induced by APO had a significant difference at 14d and 21d（P0.05）.The scoring of AIM,the duration of rotation and the time of pharmacodynamic action in 50mg/kg dose group all gradually increased,while those in 20mg/kg dose group increased after decrease;the score of each index in 20mg/kg dose group was lower than that in 50mg/kg dose group.The duration of rotation had significantdifferences at 7d,14d,17d,24d and 28d（P0.05 or P0.01）.The time of pharmacodynamic action had significant differences at 7d,14d and 28d（P0.01）.The start-up time of rotation in 20mg/kg dose group decreased after increase,but the index in 50mg/kg dose group increased after decrease.The change tendency of each index in 50mg/kg dose group was more obvious and stable.Conclusion Levodopa of 20mg/kg and 50mg/kg doses has a neurotoxic effect on the s