不同剂量左旋多巴对偏侧帕金森病大鼠行为学及多巴胺D_2受体表达数的影响

Effects of different doses of L-dopa on rotational behavior and amounts of cells expressing D_2 receptors in hemiparkinsonian rats

目的:研究不同剂量左旋多巴对偏侧帕金森病大鼠行为学及多巴胺D2受体表达数的影响,并对其相应机制进行探讨。方法:采用6-羟多巴胺(6-OHDA)制备偏侧PD大鼠模型,用免疫组化染色法检测PD模型大鼠分别给予左旋多巴不同剂量(10 mg.kg-1.d-1,50 mg.kg-1.d-1,100 mg.kg-1.d-1)腹腔注射15 d前后纹状体部位的多巴胺D2受体表达数、观察大鼠行为学改变。结果:成功PD模型大鼠30 m in旋转圈数与损毁侧及其健侧的D2受体表达数增加百分数呈线性相关(r=0.927,P<0.01),大剂量左旋多巴干预后PD大鼠的旋转圈数明显少于对照组(P<0.05),且损毁侧纹状体多巴胺D2受体表达数明显少于对照组(P<0.01)。结论:大剂量左旋多巴干预能明显改善PD大鼠的旋转行为,并使纹状体多巴胺D2受体明显下调。

AIM ： To observe the effects of different doses of L - dopa on the rotational behavior and amounts of cells expressing D2 receptors in striatum in bemiparkinsonian rats. METHODS： A hemiparkinsonian model was established in rats by pretreatment with 6 - hydroxydopamine. The D2 receptor expression were detected by immunohistochemical staining. The numbers of rotations induced by apomorphine was counted within 30 min before and after L- dopa （10 mg· kg^-1 · d^-1,50mg·kg^-1· d^-1 or 100 mg· kg^-1· d^-1, ip） was introduced to Parkinson＇s disease （PD） model rats for 15 days. RESULTS ： In successful PD model rats, the increased percentage of D2 receptor in lesioned side compared with intact side was associated linearly with the numbers of rotations within 30 min （ r =0. 927, P 〈0. 01 ）. After high dose of L - dopa intervention to PD model, the numbers of rotations decreased significantly （ P 〈 0. 05 ）, the amounts of cells expressing D2 receptor at the lesioned side striatum decreased significantly （P 〈 0. 01 ）. CONCLUSION： After high dose of L- dopa intervention, rotation behavior of PD rats improves, and D2 receptor is down - regulated significantly.