Involvement of hydroxy radical stress in neurotoxicity in rat nigrostriatal system

为了研究羟自由基应激在多巴胺能激动剂的急性和慢性给药的神经毒性中的作用，我们计划在6-羟基多巴胺（6-OHDA）的帕金森病大鼠模型中进行微透析和各种组织学研究，并进一步在模型中接受了纹状体内移植的胎儿腹侧中脑。利用微透析和HPLC-ECD技术，监测和检测了单次或重复给予L-DOPA或甲基苯丙胺（i. p.）后纹状体细胞外L-DOPA、多巴胺及其代谢产物、谷氨酸和GABA的浓度，以及灌流中羟基自由基与水杨酸反应生成2，3-二羟基苯甲酸（2，3-DHBA）的情况。我们已经研究了拓扑特异性的左旋多巴或甲基苯丙胺诱导激活的即刻早期基因蛋白质，c-Fos和Zif 268在黑质纹状体系统中的6-OHDA大鼠有或没有纹状体内移植。我们尚未完成这项研究，并正在继续进一步研究。

To examine the involvement of hydroxyl radical stress in neurotoxicity of acute and chronic administration of the dopaminergic agonists, we planed to perform the microdialysis and various kinds of histological studies in a rat model of Parkinson's disease by 6-hydroxydopamine (6-OHDA), and furthermore in the model having received intrastriatal grafts of fetal ventral mesencephalon. With the utilization of the microdialysis and HPLC-ECD, the extracellular concentration of striatal L-DOPA, dopamine, its metabolites, glutamate and GABA, and furthermore the formation of 2,3-dihydroxybenzoic acid (2,3-DHBA), derived from the reaction of hydroxyl radicals and salicylate in perfusion, were monitored and detected following single or repeated administration of L-DOPA or methamphetamine (i.p.). We have examined the topological specificity of L-DOPA- or methamphetamine-induced activation of the immediate-early gene proteins, c-Fos and Zif268 in the nigrostriatal system in the 6-OHDA rat with or without the intrastriatal grafts. We have not yet complete this study, and are continuing further study.