不同剂量左旋多巴对帕金森病大鼠行为学影响

Experimental Study on the Behavioural Effect on Rats with Pakinson-like Disease Treated by Different Doses of Levodopa

目的观察不同剂量左旋多巴治疗帕金森病(PD)的效果,并进一步探讨合理使用左旋多巴治疗PD的剂量。方法采用6-OHDA脑立体定向注射术建立大鼠PD模型,采用行为学观察法观察3种不同剂量左旋多巴[按体重10、50、100mg/(kg.d)]作用不同时间(1、3、5、7d)对PD大鼠黑质细胞毒性作用后的行为学变化以及停止左旋多巴治疗后7d各项指标的变化。结果与对照组比较,小剂量组大鼠旋转圈数随左旋多巴使用剂量和时间增加而减少,中、大剂量组大鼠旋转圈数随左旋多巴使用剂量和时间增加而增加;各组大鼠旋转启动时间随左旋多巴使用剂量和时间增加而减少,最高转速及持续时间则随使用剂量增加而增加。结论应尽可能以小剂量、间隔使用左旋多巴治疗PD。

Objective To observe the effects of different doses of [evodopa （L-dopa） on treating Parkinson-like desease （PD） model in rats and explore the dosage in which PD can be treated reasonably with L-dopa. Methods The rat model of PD were produced by injection of 6-OHDA stereotaxically to the right side of the mesencephic ventral tegmental area （VTA） and substantia nigra pars compacta （SNe）. The PD rats were treated intraperitoneally with different dosages [10, 50, 100 mg/（kg · d） of L-dopa] and in different treatment durations （1, 3, 5, 7 d）. In this study, rotation behaviour was induced by apomorphine. The extent of injury in the substantia nigra was estimated by initiating time, the maximum number of rotation, lasting time of rotation at different doses and treating durations of levodopa. Results Comparing with the control group, the extent of nigral injury of medium and large doses groups was inereased in correlated with the dosage of L-dopa. The maximum rotational speed and lasting time were increased with the elevated dosage of L-dopa. The initiating time is on the contrary. Conclusions In order to treat PD effeetively, L-dopa should be used in a safe range of dosage. The overdose L-dopa may be toxic to the rats. With small dose and treating with discontinued intervals may be the best suggestion.