Bavaresco Caren Serra, Chiarani Fabria, Wajner Moacir, Netto Carlos Alexandre, de Souza Wyse Angela Terezinha
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003 Porto Alegre, RS, Brazil.
Int J Dev Neurosci. 2006 Nov;24(7):411-7. doi: 10.1016/j.ijdevneu.2006.08.007. Epub 2006 Oct 10.
The aim of this study was to investigate the effects of a single intrastriatal injection of hypoxanthine, the major metabolite accumulating in Lesch-Nyhan disease, on Na(+),K(+)-ATPase, acetylcholinesterase and catalase activities in striatum, cerebral cortex and hippocampus of rats at different post-infusion periods. Adult Wistar rats were divided in two groups: (1) vehicle-injected group (control) and (2) hypoxanthine-injected group. For Na(+),K(+)-ATPase activity determination, the animals were sacrificed 3h, 24h and 7 days after drug infusion. For the evaluation of acetylcholinesterase and catalase activities, the animals were sacrificed 30min, 3h, 24h and 7 days after hypoxanthine infusion. Results show regional and time dependent effects of hypoxanthine on Na(+),K(+)-ATPase, acetylcholinesterase and catalase activities. The in vitro effect of hypoxanthine on the same enzymes in striatum was also investigated. Results showed that hypoxanthine inhibited Na(+),K(+)-ATPase, but not the activities of acetylcholinesterase and catalase in rat striatum. We suggest that these modification on cerebral biochemical parameters (Na(+),K(+)-ATPase, acetylcholinesterase and catalase activities) induced by intrastriatal administration of hypoxanthine in all cerebral structures studied, striatum, hippocampus and cerebral cortex, could be involved in the pathophysiology of Lesch-Nyhan disease.
本研究的目的是调查单次纹状体内注射次黄嘌呤（莱施-奈恩病中积累的主要代谢产物）对不同输注后时期大鼠纹状体、大脑皮层和海马中钠钾ATP酶、乙酰胆碱酯酶和过氧化氢酶活性的影响。成年Wistar大鼠分为两组：（1）注射溶剂组（对照组）和（2）注射次黄嘌呤组。为了测定钠钾ATP酶活性，在药物输注后3小时、24小时和7天处死动物。为了评估乙酰胆碱酯酶和过氧化氢酶活性，在注射次黄嘌呤后30分钟、3小时、24小时和7天处死动物。结果显示次黄嘌呤对钠钾ATP酶、乙酰胆碱酯酶和过氧化氢酶活性具有区域和时间依赖性影响。还研究了次黄嘌呤对纹状体中相同酶的体外作用。结果表明，次黄嘌呤抑制大鼠纹状体中的钠钾ATP酶，但不抑制乙酰胆碱酯酶和过氧化氢酶的活性。我们认为，在所有研究的脑结构（纹状体、海马和大脑皮层）中，纹状体内注射次黄嘌呤诱导的这些脑生化参数（钠钾ATP酶、乙酰胆碱酯酶和过氧化氢酶活性）的改变可能与莱施-奈恩病的病理生理学有关。
