不同剂量左旋多巴对帕金森病运动并发症大鼠模型行为学的影响

The Comparison of the Severity of Motor Complications in Rat Model of Parkinson's Disease Treated with Different Doses of Levodopa

目的:比较不同剂量左旋多巴长期注射对帕金森病(PD)运动并发症大鼠模型异常不自主运动(AIM)和疗效减退的影响,以确定合适的左旋多巴用药剂量和行为学评价标准。方法:立体定向SD大鼠右侧前脑内侧束,注射6羟基多巴建立PD大鼠模型。成模PD大鼠随机分为3组,分别腹腔注射左旋多巴酯:小剂量组(20mg·kg^(-1)·d^(-1))、中剂量组(50mg·kg^(-1)·d^(-1))和大剂量组(100mg·kg^(-1)·d^(-1)),每天2次,持续21d。比较3组PD大鼠模型AIM各组份的评分情况及对侧旋转反应时间。结果:左旋多巴3种剂量均可诱发PD大鼠出现相似程度的口面、前肢、轴向AIM,但大剂量组大鼠旋转AIM的评分高于小剂量组(P<0.05),且旋转反应时间缩短幅度大于中剂量组和小剂量组(P<0.05)。结论:小剂量左旋多巴就可诱发PD大鼠出现明显的AIM,又能避免过于剧烈的旋转运动对AIM评分的干扰;但观察疗效减退现象需要选用大剂量左旋多巴以诱导出稳定下降的旋转反应时间。

Aim：To evaluate the impact of different doses of levodopa on abnormal involuntary movement and rotational duration in rat model of Parkinson＇s disease.Methods：The hemi-parkinsonian rat model was produced by stereotaxically injecting 6-OHDA to right medial forebrain bundle（MFB）.The PD rats were divided into three groups and separately intraperitoneally treated with varied doses of levodopa（20,50 or 100 mg-kg^（-1）·d^（-1）） twice daily for 21 days.Abnormal involuntary movements and rotational duration were assessed. Abnormal involuntary movements were measured for forelimb,axial,orolingual,and rotational movements individually.Results：The three levodopa doses induced similar severity of forelimb,axial,oroUngual AIM in PD rat model.Rats treated with 100 and 50 mg-kg^（-1）·d^（-1） doses of L-dopa displayed generally high rotational AIMs than did animals treated with 20 mg-kg^（-1）·d^（-1）（P0.05）.And the high dose of L-dopa induced more evident shortening of rotational duration than did animals treated with the low dose.Conclusion：Contrary to axial, forelimb and orolingual AIMs,rotational AIMs seemed to provide a correlate of contralateral rotation and did not represent a specific measure of dyskinetic motor features.It is recommended to chose the 20 mg·kg^（-1）·d^（-1） usage to induce AIM behavior in PD rat model to avoid the interruption of intensive rotational behavior;but it is needed to use high dosage of levodopa to induce stable and progressive shortening of rotational duration to mimic the wearing off symptoms.