培高利特对帕金森病大鼠保护作用的实验研究

Protective effect of pergolide on parkinsonian model rats

目的 探讨多巴胺受体激动剂培高利特 (pergolide)对帕金森病 (PD)模型大鼠的抗氧化作用及其机制。方法 Wistar大鼠随机分为 4组 (对照组和 3个实验组 ) ,实验组预先于腹腔内分别注射培高利特 (1 0mg·kg-1)、选择性D2 受体拮抗剂氨黄酰基苯甲酰胺化合物 (Sulpiride ,2 5mg·kg-1)及培高利特 +Sulpiride。各组预处理均 1次 /天 ,连续 7d后 ,每组大鼠各取 6只分离纹状体 ,测定抗氧化物SOD及GSH活性。各组所剩大鼠则通过立体定位注射 6 羟基多巴胺 (6 OHDA)制作PD模型 ,两周后比较各组阿朴吗啡诱导的旋转行为 ,并取损伤侧纹状体测定多巴胺 (DA)及其代谢产物多巴克 (DOPAC)、高香草酸 (HVA)的含量。结果 大鼠预先连续注射培高利特 7天 ,可明显增强纹状体SOD及GSH的活性 (P <0 0 5 ) ,并对抗 6 OHDA损伤后纹状体DA及其代谢产物含量的下降 (P <0 0 1) ,降低阿朴吗啡诱导的旋转行为 (P <0 0 5 )。而同时应用Sulpiride可抑制培高利特的促纹状体抗氧化作用 ,并消除其对DA能神经元的保护效应。结论 培高利特可通过增加纹状体抗氧化能力 ,对纹状体DA能神经元提供保护作用 ,其机制可能主要与刺激DAD2 受体有关。

Aim To explore the antioxidation of pergolide on rat models of Parkinson disease and its mechanism. Methods Wistar rats were pretreated daily with pergolide(1.0 mg·kg -1,ip),pergolide combined with sulpiride(25 mg·kg -1) or sulpiride alone for 7 days, and then sacrificed by decapitation. The activity of SOD and GSH in striatum was determined. Unilateral Parkinsonian models were made in rest of the rats by stereotaxically injecting 6-OHDA. After two weeks, apomorphine (APO)-induced rotational behavior of each group was compared, and the concentrations of striatal dopamine (DA),dihydroxyphenyl acetic acid(DOPAC) and homovanilic acid(HVA) were determined by high performance liquid chromatography (HPLC). Result Administration of pergolide for 7 days significantly increased the act- ivities of SOD and GSH in the striatum (P<0.05),and protected aga inst reduction of D A and its metabolites in striatum two weeks after 6-OHDA injection (P<0.01 ).The APO-induced rotational behavior was significantly decreased (P<0.05) . Pretreatment with sulpiride prevented pergolide from enhancing activities of s triatal SOD and GSH, and abolished its protective effect on DA neurons against 6-OHDA-induced lesion.Conclusion Pergolide could provide neur oprotection to DA neuron,and increment of striatal antioxidative activity. Stim ulation of the DA D 2 receptor may be its principal underlying mechanism.