Biopterin in the acute phase of hypoxia-ischemia in a neonatal pig model
Biopterin in the acute phase of hypoxia-ischemia in a neonatal pig model
复制标题
DOI：
10.1016/j.braindev.2007.04.009
复制
发表时间：
2008-01-01
影响因子：
1.7
通讯作者：
Yamano, Tsunekazu
中科院分区：
文献类型：
--
作者：
Fujioka, Hiroki;Shintaku, Haruo;Yamano, Tsunekazu
为了阐明诱导型一氧化氮合酶（inducible NOS，iNOS）在缺氧缺血性脑损伤中的作用，我们在新生仔猪模型中检测了iNOS及其四氢生物蝶呤辅因子在大脑皮层和血浆中的表达。我们还研究了低温在NOS表达和生物蝶呤产生中的作用。雄性新生仔猪经6%氧气通气45 min后，在缺氧期间夹闭颈总动脉。HI组给予30%氧复苏。亚低温组与HI组相同，在缺氧缺血损伤后将其身体冷却至35.5 ℃。还保留了假手术处理的仔猪。HI组损伤后12 h，iNOS表达于大脑皮质神经元和巨噬细胞。缺氧缺血12 h后大脑皮层亚硝酸盐和硝酸盐浓度升高，但生物蝶呤水平无变化。损伤后的血浆生物蝶呤浓度（377.9 +/- 78.7 nM）比损伤前（80.1 +/- 4.3 nM）高5倍;该水平在损伤后4 h达到峰值（604.8 +/- 200.9 nM），12 h后仅略有下降（445.9 +/- 57.8 nM）。低温组损伤后12 h未见iNOS表达。损伤后的血浆生物蝶呤浓度（464.2 +/- 92.3 nM）与HI组相似，但被4 h低温抑制（229.3 +/- 106.8 nM）。本研究发现，在急性缺氧缺血时，神经元iNOS的表达和NO的产生增加。脑生物蝶呤没有增加，虽然在缺氧缺血血浆生物蝶呤升高5倍。这种差异也可能影响缺氧缺血性器官损伤。(c)2007 Elsevier B. V.保留所有权利。
To clarify the participation of inducible NOS (iNOS) in the hypoxia-ischemia, we examined iNOS and its tetrahydrobiopterin cofactor in the cerebral cortex and plasma in a newborn-piglet model. We also investigated the role of hypothermia in NOS expression and biopterin production. Male newborn piglets were ventilated 6% oxygen for 45 min. Their common carotid arteries were clamped during hypoxia. Then they were resuscitated with 30% oxygen (HI group). Piglets of the hypothermia group were treated as the HI group and their body was cooled to 35.5 degrees C after hypoxic-ischemic insults. Sham-treated piglets were also reserved. In the HI group, iNOS was present in neurons and macrophages of the cerebral cortex 12 h after the insult. The concentrations of nitrite and nitrate were elevated in the cerebral cortex 12 h after hypoxic-ischemic insults but the biopterin level was unchanged. The plasma biopterin concentration after the insult (377.9 +/- 78.7 nM) was five times higher than before the insult (80.1 +/- 4.3 nM); this level peaked 4 h after the insult (604.8 +/- 200.9 nM) and only slightly decreased after 12 h (445.9 +/- 57.8 nM). In the hypothermia group, no iNOS expression was observed 12 h after the insult. The plasma biopterin concentration after the insult (464.2 +/- 92.3 nM) was similar to that in the HI group, but was suppressed by 4 h of hypothermia (229.3 +/- 106.8 nM). In this study, neuronal iNOS expression and increase of NO production were found in the acute phase of hypoxia-ischemia. Brain biopterin did not increase in hypoxia-ischemia although plasma biopterin was five-fold elevated. The discrepancy may also affect hypoxic-ischemic organ damage. (c) 2007 Elsevier B.V. All rights reserved.