论文部分内容阅读
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。
OBJECTIVE: To compare the effects of different doses of levodopa long-term injection on abnormal involuntary movement (AIM) and diminished efficacy of Parkinson’s disease (PD) in rats to determine the appropriate dose and behavioral evaluation criteria for levodopa . Methods: The right lateral forebrain of SD rats was stereotacticly injected with 6-hydroxydopamine to establish a rat model of PD. The model rats were randomly divided into 3 groups, and were given intraperitoneal injection of levodopa: low dose (20 mg · kg -1 · d -1) and middle dose (50 mg · kg - 1) · d -1 and 100 mg · kg -1 · d -1 twice daily for 21 days. The scores of AIM components and contralateral rotation response time in the three groups of PD rats were compared. RESULTS: All the three doses of levodopa induced a similar degree of oral, forelimb and axial AIM in PD rats, but the AIM scores of rats in high-dose group were higher than those in the low-dose group (P <0.05) Response time was shorter than the middle dose group and the low dose group (P <0.05). CONCLUSIONS: Low-dose levodopa can induce obvious AIM in PD rats and avoid the disturbance of AIM score caused by too violent rotational movement. However, it is necessary to select high-dose levodopa to induce a steady decline Rotation reaction time.