摘要
Objective The aim of the present study was not only to assess the retrograde degenerative changes in the dopaminergic neurons of the substantia nigra （SN） and ventral tegmental area （VTA） after injection of 6-hydroxydopamine （6-OHDA） into the striatum, but also to use this 6-OHDA model of Parkinson＇s disease to explore the possible neuroprotective effect of R-apomorphine （R-APt）. Methods The partial lesion was obtained by intrastriatal administration of 6-OHDA. R- APt administration （10 mg/kg, s.c.） started 15 min prior to lesioning and continued daily for another 22 days post surgery. Testing was carried out 5 weeks after lesioning. We investigated the histology and associated behavior and neurochemical changes. Structural and functional deficits were quantified by tyrosine hydroxylase （TH） / Nissl-staining cell number counting, striatal dopamine （DA） content determination and amphetamine-induced rotation analysis. Results R-APt- treatment attenuated the amphetamine-induced ipsiversive rotation 5 weeks after the lesion induction. R-APt administra- tion for 22 days significantly reduced the size of the lesion at the level of the SN from 50% （control group） to 69%. Moreover, the cell shape resembled that observed in the intact animals. R-APt treatment significantly increased the number of cells in both the lesion and the intact sides of VTA by 60%, suggesting selective neurotrophic effect of R-APt in this area. Finally, R-APt-treatment significantly attenuated the 6-OHDA-induced striatal DA depletion and normalized dihydroxyphenylacetic acid （DOPAC）/DA ratios. Conclusion We conclude that R-APt has neuroprotective and pos- sible neurotrophic effect on a striatal lesion with 6-OHDA, suggesting that this drug may have rescuing properties in patients with early stage Parkinson＇s disease. These effects are more pronounced in VTA and enhance with duration of treatment.
目的本研究旨在评定6-羟基多巴损伤纹状体后黑质和腹侧被盖区的变化,并探讨阿扑吗啡在该模型中可能存在的神经保护作用。方法6-羟基多巴损伤纹状体模型:在造模前15分钟,连续22天皮下注射阿扑吗啡10 mg/kg·d。在第5 周时,观察大鼠行为学(安啡他明诱导的旋转数目)、组织化学(TH/Nissl 染色后黑质和腹侧被盖区的多巴胺细胞)、神经化学(高压液相法测定纹状体的多巴胺含量)改变。结果阿扑吗啡不仅消弱安啡他明诱导的旋转数目,而且,显著减少黑质的损伤(与对照组相比,多巴胺细胞达到69%,细胞形态恢复正常)和腹侧被盖区的损伤(多巴胺细胞增加了60%,细胞形态恢复正常); 并且,阿扑吗啡显著消弱6-羟基多巴损伤纹状体的多巴胺含量,使DOPAC/DA率恢复正常。结论在6-羟基多巴损伤纹状体模型中,阿扑吗啡不仅有神经保护作用,而且有神经营养作用。但神经营养作用局限于腹侧被盖区,并随着用药时间延长而增加。
