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一氧化氮对子宫内受照射发育中大鼠脑的早期神经保护作用。

Early neuroprotective effect of nitric oxide in developing rat brain irradiated in utero.

作者信息

Gisone Pablo, Boveris Alejandro D, Dubner Diana, Perez María Rosario, Robello Elizabeth, Puntarulo Susana

机构信息

Laboratorio de Radiopatología, Autoridad Regulatoria Nuclear, Buenos Aires, Argentina.

出版信息

Neurotoxicology. 2003 Mar;24(2):245-53. doi: 10.1016/S0161-813X(02)00166-3.

DOI:10.1016/S0161-813X(02)00166-3
PMID:12606296
Abstract

Pregnant Wistar rats were exposed on day 17 of gestation to 1 Gy gamma irradiation from a Co(60) source. Even though it is established that gamma radiation-dependent damage is mainly due to free radical generation neither the ascorbyl radical/ascorbate ratio nor the lipid radical content in developing rat brain were affected by prenatal irradiation. A distinctive EPR signal for the adduct NO-Fe-MGD (g=2.03 and a(N)=12.5 G) was detected in brain homogenates prepared from irradiated rats. Nitric oxide (NO)-dependent EPR signal increased in a time-dependent manner up to 2h post-irradiation. NO concentration in unirradiated brains was 37+/-4 pmol/g brain and 45+/-2, 77+/-5 and 216+/-6 after 30, 60 and 120 min post-irradiation, respectively. Total nitric oxide synthase activity was increased by 77 and 51% after 30 and 60 min post-irradiation, respectively, and returned to control values after 120 min. Thus, increased NO steady-state concentration could be ascribed to an increase in NOS activity. Taken as a whole, these results suggest that NO might act to protect the developing brain from the cytotoxicity of reactive species.

摘要

妊娠第17天的Wistar大鼠暴露于来自钴(60)源的1 Gyγ射线照射下。尽管已经确定γ射线依赖性损伤主要是由于自由基的产生,但发育中大鼠大脑中的抗坏血酸自由基/抗坏血酸比率和脂质自由基含量均未受到产前照射的影响。在从受照射大鼠制备的脑匀浆中检测到加合物NO-Fe-MGD的独特电子顺磁共振信号(g = 2.03,a(N)= 12.5 G)。依赖于一氧化氮(NO)的电子顺磁共振信号在照射后2小时内呈时间依赖性增加。未照射大脑中的NO浓度为37±4 pmol/g脑,照射后30、60和120分钟分别为45±2、77±5和216±6。照射后30和60分钟,总一氧化氮合酶活性分别增加了77%和51%,120分钟后恢复到对照值。因此,NO稳态浓度的增加可能归因于一氧化氮合酶活性的增加。总体而言,这些结果表明NO可能起到保护发育中的大脑免受活性物质细胞毒性的作用。

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