Relationships of dopamine, cortical oxygen pressure, and hydroxyl radicals in brain of newborn piglets during hypoxia and posthypoxic recovery.
Relationships of dopamine, cortical oxygen pressure, and hydroxyl radicals in brain of newborn piglets during hypoxia and posthypoxic recovery.
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新生仔猪缺氧及缺氧恢复过程中脑内多巴胺、皮质氧压及羟自由基的关系
DOI：
10.1046/j.1471-4159.1995.65031205.x
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发表时间：
1995
影响因子：
4.7
通讯作者：
Pastuszko,A
中科院分区：
文献类型：
--
作者：
Olano,M;Song,D;Murphy,S;Wilson,DF;Pastuszko,A
本研究描述了新生仔猪缺氧和缺氧后复氧期间细胞外纹状体多巴胺、皮质氧压和纹状体羟自由基的关系。通过将吸入氧 (FiO2) 分数从 22%（对照）减少到 7% 1 小时来诱导缺氧。然后 FiO2 返回到控制值并继续测量 2 小时。通过磷光的氧依赖性猝灭来测量脑氧压，并通过体内微透析测定纹状体中多巴胺、3,4-二羟基苯乙酸（DOPAC）、高香草酸（HVA）的细胞外水平和羟基自由基。缺氧使皮质氧压从 47 ± 2 降低至 9 ± 1.3 托 (p< 0.001)；纹状体中细胞外多巴胺的水平增加至对照的 16,000 ± 3,270%（p < 0.01），而 DOPAC 和 HVA 的水平分别下降至对照的 25.3 ± 6%（p < 0.001）和 36 ± 5%（p < 0.01）。与对照组相比，缺氧期间每个时间点的羟自由基水平并未显着增加，但测量值的总和显着增加（p<0.05）。在 FiO2 恢复到 22% 后的前 5 分钟内，皮质氧分压增加至控制值，并在剩余的测量期间保持在该水平。在 40 分钟的复氧过程中，细胞外多巴胺水平下降至与对照无统计学差异的值。在复氧的前 10 分钟内，DOPAC 和 HVA 进一步下降，然后开始缓慢增加。复氧 70 分钟后，这些值与对照没有显着差异。在整个再充氧期间，羟基自由基均高于对照，在再充氧 100 分钟后观察到最大值。在缺氧前 5 小时给动物注射 α-甲基-p-酪氨酸，这种增加在很大程度上被消除了，这一过程会耗尽大脑中的多巴胺。我们的结果表明，缺氧后复氧过程中纹状体多巴胺的氧化至少是观察到的纹状体羟自由基水平增加的部分原因，这可能会加剧缺氧后脑损伤。
The present study describes the relationships of extracellular striatal dopamine, cortical oxygen pressure, and striatal hydroxyl radicals in brain of newborn piglets during hypoxia and posthypoxic reoxygenation. Hypoxia was induced by reducing the fraction of inspired oxygen (FiO2) from 22% (control) to 7% for 1 h. The FiO2was then returned to the control value and measurements were continued for 2 h. Cerebral oxygen pressure was measured by the oxygen dependent quenching of phosphorescence and extracellular levels of dopamine, 3,4‐dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and hydroxy radicals in the striatum were determined by in vivo microdialysis. Hypoxia decreased the cortical oxygen pressure from 47 ± 2 to 9 ± 1.3 torr (p< 0.001); the levels of extracellular dopamine in the striatum increased to 16,000 ± 3,270% of control (p< 0.01), whereas the levels of DOPAC and HVA decreased to 25.3 ± 6% (p< 0.001) and 36 ± 5% (p< 0.01) of control, respectively. Compared with control, the hydroxyl radical levels at each time point were not significantly increased during hypoxia, although the sum of the measured values was significantly increased (p< 0.05). During the first 5 min after FiO2was returned to 22%, the cortical oxygen pressure increased to control values and stayed at this level for the remainder of the measurement period. The extracellular level of dopamine declined to values not statistically different from control during 40 min of reoxygenation. During the first 10 min of reoxygenation, DOPAC and HVA further decreased and then began to slowly increase. By 70 min of reoxygenation, the values were not significantly different from control. Hydroxyl radicals were above control during the entire period of reoxygenation, with maximal values observed after 100 min of reoxygenation. This increase was largely abolished by injecting the animals with α‐methyl‐p‐tyrosine 5 h before hypoxia, a procedure that depleted the brain of dopamine. Our results suggest that oxidation of striatal dopamine during posthypoxic reoxygenation is at least partly responsible for the observed increase in striatal level of hydroxyl radicals that may exacerbate posthypoxic cerebral injury.