帕金森病大鼠模型纹状体中谷氨酸、γ-氨基丁酸与多巴胺之间的关系

Relationship between glutamate,GABA and dopamine in striatum of a rat model of Parkinson's disease

目的:了解帕金森病大鼠模型纹状体内谷氨酸(glutamate,Glu)、γ-氨基丁酸(gama-aminobutyric acid,GABA)和多巴胺(dopamine,DA)之间的关系,从而进一步探讨帕金森病的发病机制。方法:动物分为溶剂对照组、假手术组和帕金森模型组。大脑右侧黑质致密部和前脑内侧束两点注射6-羟基多巴胺(6-hydroxydopamine,6-OHDA)建立帕金森病大鼠模型,溶剂对照组注入生理盐水,假手术组不注射任何药物,采用脑微透析术于建模后第3,4,5,6周连续动态透析大鼠毁损侧纹状体,结合高效液相色谱(HPLC)动态监测各组谷氨酸、GABA和多巴胺的变化。结果:(1)PD组纹状体内多巴胺含量到第5周仅为溶剂对照组和假手术组的1/5;(2)谷氨酸含量随建模时间逐渐升高,到第6周PD组是溶剂对照组和假手术组的1倍以上;(3)GABA含量呈下降趋势,到第6周约降至溶剂对照组、假手术组的1/2。结论:帕金森病大鼠模型纹状体内谷氨酸的变化与多巴胺分泌可能存在某种联系;GABA含量随建模时间的增加而下降。

Objective： To explore the relationship among striatum glutamate（Glu）,gama-aminobutyric acid（GABA） and dopamine in a rat model of 6-OHDA-induced Parkinson＇s disease,so as to study the pathogenesis of Parkinson＇s disease.Methods：The rats were divided to 3 groups： vechicle,sham and Parkinson＇s disease model（PD）.PD rat model was developed by stereotaxic injection of 6-OHDA into substantia nigra pars compcata（SNC） and medial forebrain bundle（MFB） on the right side of the brain.Rats of vechicle group received saline injection and sham group model received no injection.Brain microdialysis combined with high-performance liquid chromatography（HPLC） was applied to detect dopamine,glutamate,GABA levels in the lesioned striatum at 3,4,5,6 weeks post-lesion.Results：（1） Dopamine content in PD group decreased markedly,which was one-fifth of that in vehicle and sham group at 5 weeks post-lesion;（2）Glutamate content in PD group increased over time and was over one time as high as that in other groups at 6 weeks post-lesion;（3）GABA level at 6 weeks in PD group dropped to one half of that in vechicle and sham groups.Conclusion： These data suggest that Glu release might be associated with dopamine level,and GABA level dropped over time from the onset of Parkinson＇s disease.