脑片在诱导型一氧化氮合酶在脑缺血再灌注中的致病作用研究中的应用。

Use of brain slices in the study of pathogenic role of inducible nitric oxide synthase in cerebral ischemia-reperfusion.

作者信息

De Alba J, Cárdenas A, Moro M A, Leza J C, Lorenzo P, Lizasoain I

机构信息

Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Spain.

出版信息

Gen Pharmacol. 1999 May;32(5):577-81. doi: 10.1016/s0306-3623(98)00280-8.

DOI:10.1016/s0306-3623(98)00280-8

PMID:10382860

Abstract

We have recently demonstrated that inducible nitric oxide synthase (iNOS) is expressed in rat forebrain slices exposed to oxygen and glucose deprivation (OGD). Now, we have found that the expression of iNOS after OGD is time-dependent since 20 min of OGD produces the appearance of iNOS at earlier times than 10 min of OGD. OGD also causes neurotoxicity in this model, as revealed by the increase in excitatory amino acid, neuron specific enolase and lactate dehydrogenase (LDH) efflux to the incubation solution. Finally, the administration of the NMDA receptor antagonist MK-801 (100 nM) inhibits both the expression of iNOS and the release of LDH. Our findings demonstrate that this method may be considered an useful in vitro model of ischemia-reperfusion to determine the therapeutic role of neuroprotective tools.

摘要

我们最近证明，诱导型一氧化氮合酶（iNOS）在暴露于氧糖剥夺（OGD）的大鼠前脑切片中表达。现在，我们发现OGD后iNOS的表达呈时间依赖性，因为20分钟的OGD比10分钟的OGD在更早的时间点产生iNOS。在该模型中，OGD还会导致神经毒性，这可通过孵育溶液中兴奋性氨基酸、神经元特异性烯醇化酶和乳酸脱氢酶（LDH）外流的增加来揭示。最后，给予NMDA受体拮抗剂MK-801（100 nM）可抑制iNOS的表达和LDH的释放。我们的研究结果表明，该方法可被视为一种有用的体外缺血再灌注模型，以确定神经保护工具的治疗作用。