Izumi Y, Benz A M, Clifford D B, Zorumski C F
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63100.
Exp Neurol. 1993 May;121(1):14-23. doi: 10.1006/exnr.1993.1067.
To investigate the possible role of nitric oxide (NO) in n-methyl-D-aspartate (NMDA)-induced neurotoxicity we examined the effects of sodium nitroprusside (SNP) in rat hippocampal slices. Incubation with 3 mM SNP for up to 2 h produced neuronal damage characterized by "nuclear ballooning" in CA3 and CA1 pyramidal neurons and interneurons. The nuclear ballooning was not blocked by lowering the external calcium concentration or coincubation with MK-801 and/or 6,7-dinitro-quinoxaline-2,3-dione. Two lines of evidence suggest that the SNP neurotoxicity is not mediated by NO. First, inactivation of SNP by UV light failed to prevent the nuclear ballooning. Second, the toxicity was not attenuated by coadministration of hemoglobin. Although cyanide can be released from SNP, potassium cyanide did not mimic the nuclear ballooning. In electrophysiological experiments, 100 microM SNP irreversibly diminished the CA1 population spike amplitude while having less effect on the field excitatory postsynaptic potential. The effect of SNP on population spikes was inhibited by hemoglobin and was not mimicked by light-inactivated SNP. These results suggest that active SNP and light-treated SNP have different effects on hippocampal neurons and that SNP induces damage that differs from that produced by NMDA or cyanide.
为了研究一氧化氮（NO）在N-甲基-D-天冬氨酸（NMDA）诱导的神经毒性中可能发挥的作用，我们检测了硝普钠（SNP）对大鼠海马切片的影响。用3 mM SNP孵育长达2小时会导致神经元损伤，其特征为CA3和CA1锥体神经元以及中间神经元出现“核肿胀”。降低细胞外钙浓度或与MK-801和/或6,7-二硝基喹喔啉-2,3-二酮共同孵育并不能阻止核肿胀。有两条证据表明SNP的神经毒性不是由NO介导的。第一，紫外线使SNP失活并不能防止核肿胀。第二，同时给予血红蛋白并不能减轻毒性。尽管氰化物可从SNP中释放出来，但氰化钾并不会模拟核肿胀现象。在电生理实验中，100 microM的SNP可不可逆地降低CA1群体峰电位幅度，而对场兴奋性突触后电位的影响较小。SNP对群体峰电位的作用可被血红蛋白抑制，且光灭活的SNP不会模拟这种作用。这些结果表明，活性SNP和经光处理的SNP对海马神经元有不同影响，且SNP诱导的损伤与NMDA或氰化物所致损伤不同。
