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采用微透析和高效液相色谱-电化学(HPLC-ECD)技术研究了谷氨酸和MK-801对正常和帕金森模型大鼠纹状体内多巴胺代谢的影响。用微透析技术在大鼠纹状体内分别定位给以左旋多巴、L-谷氨酸和/或MK-801,同时收集透析液,用HPLC-ECD方法测定透析液中多巴胺代谢产物的浓度。微透析和HPLC-ECD分析结果表明:纹状体内定位给以左旋多巴,正常大鼠和帕金森模型大鼠纹状体内多巴胺代谢产物的浓度均升高;纹状体内定位给以L-谷氨酸,可使正常大鼠纹状体内多巴胺代谢产物的浓度降低,但对帕金森大鼠模型纹状体内多巴胺代谢产物浓度的降低不显著;纹状体内定位给以MK-801,正常大鼠纹状体内多巴胺代谢产物的浓度升高;但对帕金森大鼠模型纹状体内多巴胺代谢产物浓度的升高不显著;纹状体内同时定位给以MK-801和L-谷氨酸,可以有效防止L-谷氨酸所致正常大鼠纹状体内多巴胺代谢产物浓度的降低。结果提示,谷氨酸可以通过NMDA受体调节多巴胺的代谢。尽管非竞争性NMDA拈抗剂MK-801可以有效防止L-谷氨酸所致正常大鼠纹状体内多巴胺代谢产物浓度的降低,但却不能有效地改善帕金森大鼠模型纹状体内多巴胺的代谢水平。因此在正常及帕金森病情况下,谷氨酸-多巴胺相互作用机制和MK-801改善帕金森病的机制还有待进一步研究。
The effects of glutamate and MK-801 on dopamine metabolism in the striatum of normal and Parkinsonian rats were studied by microdialysis and high performance liquid chromatography-electrochemistry (HPLC-ECD). Dopamine, L-glutamic acid and / or MK-801 were respectively located in the striatum of rats by microdialysis technique, dialysate was collected simultaneously, and the concentration of dopamine metabolites in dialysate was determined by HPLC-ECD method. The results of microdialysis and HPLC-ECD analysis showed that the concentration of dopamine metabolites in the striatum of levodopa, normal rats and Parkinson’s model rats were all increased in the striatum; The level of dopamine metabolites in the striatum of normal rats was decreased, but the concentration of dopamine metabolites in the striatum of Parkinson’s rats was not significantly reduced. The concentration of dopamine metabolites in the striatum increased; however, the increase of dopamine metabolites in the striatum was not significant in Parkinson’s rat model; simultaneous administration of MK-801 and L-glutamic acid in the striatum was effective Prevent the normal rat striatum caused by L-glutamic acid to reduce the concentration of dopamine metabolites. The results suggest that glutamate can regulate dopamine metabolism through NMDA receptors. Although noncompetitive NMDA antagonist MK-801 can effectively prevent the decrease of dopamine metabolite concentration in normal rat striatum induced by L-glutamic acid, it can not effectively improve the dopamine level in the striatum of Parkinson’s rat model Metabolic level. Therefore, in normal and Parkinson’s disease, glutamate-dopamine interaction mechanism and MK-801 to improve the mechanism of Parkinson’s disease remains to be further studied.