阿扑吗啡对6-羟基多巴胺毁损纹状体鼠的神经保护和神经营养作用

目的在6-羟基多巴胺毁损纹状体鼠模型上,探讨阿扑吗啡的神经保护和神经营养作用。方法用6-羟基多巴胺毁损大鼠单侧纹状体,在毁损前15 m in注射阿扑吗啡(10 mg/kg,s.c.),连续注射11 d。毁损2周后,分别进行行为学(苯丙胺引起的旋转数目)、组织学(黑质和腹侧被盖区的酪氨酸羟化酶阳性细胞计数)的观察。结果阿扑吗啡降低苯丙胺引起的向损伤侧旋转的次数,显著降低黑质神经元的损伤(从50%降至30%)。且多巴胺细胞形状可恢复到类似正常组;阿扑吗啡对正常鼠黑质细胞数无影响,但可使腹侧被盖区细胞数显著增高37%。结论阿扑吗啡对6-羟基多巴胺毁损纹状体模型鼠的黑质和腹侧被盖区神经细胞具有显著的保护作用,且改善运动功能。同时,对正常鼠的腹侧被盖区也显示神经营养作用。

Neuroprotection and neurotrophic effect of apomorphine in 6-hydroxydopamine induced striatum injury of rat

Objective To investigate the possible neuroprotective and neurotrophic effect of the R-apomorphine(R-APO) in 6-hydroxydopamine-induced striatum injury of rat.Methods The rats received a unilateral 6-hydroxydopamine(6-OHDA) injection into the striatum.R-APO administration((10 mg/kg,) s.c.) started(15 min) before 6-OHDA-injection,received R-APO for 11 days.Testing was carried out 2 weeks after lesioning.Motor impairment was evaluated by amphetamine-induced rotation.The degree of the lesion was determined by counting the amount of cell at the level of the SN and the ventral tegmental area(VTA) after tyrosine hydroxylase(TH) staining.Results(R-APO)-treatment,not only attenuated the amphetamine-induced ipsiversive rotation,but also significantly reduced the size of the lesion at the level of the SN from 50%(control group) to 30%.Moreover,the DA neuron cell morphology and size resembled that observed in intact animals.R-APO treatment had no effect on the number of cells in the SN of intact rats,but significantly increased the number of cells in the VTA.Conclusion In this lesion model for PD,R-APO treatment not only provided significant protection of the nigral cell bodies,but also improved motor function.In intact rats,we also showed neurotrophic effects of the R-APO treatment in VTA.