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依布硒啉对氧糖剥夺大鼠海马脑片的神经保护作用:与诱导型一氧化氮合酶免疫含量的相关性

Neuroprotective effect of ebselen on rat hippocampal slices submitted to oxygen-glucose deprivation: correlation with immunocontent of inducible nitric oxide synthase.

作者信息

Porciúncula Lisiane O, Rocha João Batista T, Cimarosti Helena, Vinadé Lúcia, Ghisleni Gabriele, Salbego Christianne G, Souza Diogo O

机构信息

Departamento de Bioqui;mica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - anexo, 90035-003, Porto Alegre, RS, Brazil.

出版信息

Neurosci Lett. 2003 Jul 31;346(1-2):101-4. doi: 10.1016/s0304-3940(03)00580-9.

Abstract

Ebselen is a seleno organic compound with antioxidant and anti-inflammatory properties, which is under clinical trials for the treatment of ischemic stroke. In this study, we attempted to correlate the protective effects of ebselen and the inducible nitric oxide synthase (iNOS) immunocontent in hippocampal slices submitted to oxygen-glucose deprivation (OGD), since the exacerbated production of nitric oxide by iNOS plays a role in the mechanisms of cellular death in ischemic insults. Ebselen (10 microM) protected slices from the deleterious effects of OGD (as assessed by MTT assay) only when present during all the recovery period (180 min). Moreover, ebselen added 5 and 15 min after the beginning of recovery only partially protected the slices from cellular death, while when added 30 min after the beginning of recovery no protection was observed. OGD increased the immunocontent of iNOS, and this increase was abolished also only when ebselen was present during all the recovery period. Our results indicate that the neuroprotective effect of ebselen could be related to this decrease in the iNOS immunocontent.

摘要

依布硒啉是一种具有抗氧化和抗炎特性的有机硒化合物,目前正处于治疗缺血性中风的临床试验阶段。在本研究中,我们试图将依布硒啉的保护作用与在氧-葡萄糖剥夺(OGD)条件下海马切片中诱导型一氧化氮合酶(iNOS)的免疫含量相关联,因为iNOS产生的一氧化氮过量在缺血性损伤的细胞死亡机制中起作用。依布硒啉(10微摩尔)仅在整个恢复期(180分钟)存在时才能保护切片免受OGD的有害影响(通过MTT法评估)。此外,在恢复开始后5分钟和15分钟添加依布硒啉只能部分保护切片免于细胞死亡,而在恢复开始后30分钟添加则未观察到保护作用。OGD增加了iNOS的免疫含量,并且只有在整个恢复期都存在依布硒啉时,这种增加才会被消除。我们的结果表明,依布硒啉的神经保护作用可能与此iNOS免疫含量的降低有关。

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