An in vitro model of aneurysmal subarachnoid hemorrhage:: oxidation of unconjugated bilirubin by cytochrome oxidase
An in vitro model of aneurysmal subarachnoid hemorrhage:: oxidation of unconjugated bilirubin by cytochrome oxidase
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DOI：
10.1111/j.1471-4159.2007.04667.x
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发表时间：
2007-09-01
影响因子：
4.7
通讯作者：
Clark, Joseph F.
中科院分区：
文献类型：
--
作者：
Loftspring, Matthew C.;Wurster, William L.;Clark, Joseph F.
动脉瘤性蛛网膜下腔出血是一种卒中亚型，具有较高的死亡率和致残率。脑血管痉挛可导致缺血性损伤或死亡，是动脉瘤性蛛网膜下腔出血的常见并发症，通常发生在3-9天后。血管痉挛的原因尚不清楚。最近，有强有力的证据表明胆红素的血管活性氧化产物可能参与了胆红素的生成。目前，导致胆红素氧化的因素尚不清楚。在这项研究中，我们设计了一个出血性中风的体外模型，以探讨促进胆红素氧化形成血管活性化合物的条件。使用我们的模型，我们创建了一个基本的血肿系统，包括血液、脑脊液和血红素氧合酶-1。我们以不同的方式操纵这个系统，培养它，并确定由此产生的血管活性胆红素氧化产物的浓度。刺激细胞色素氧化酶的条件使胆红素氧化产物增加(碱性反应的胆红素氧化产物分别为292.6+/-39.9mU/L和79.3+/-1.3mU/L，p<；0.05)，而氰化物可使其减弱。我们的数据表明，胆红素氧化产物可能是通过氧化(S)产生的，需要一种像细胞色素氧化酶一样的氧气利用酶。
Aneurysmal subarachnoid hemorrhage is a stroke subtype with high rates of mortality and morbidity. Cerebral vasospasm can lead to ischemic injury or death and is a common complication of aneurysmal subarachnoid hemorrhage, usually occurring 3-9 days afterwards. The cause of vasospasm is not known. Recently, there has been strong evidence that vasoactive oxidation products of bilirubin may be involved. Currently, the factors that lead to bilirubin oxidation are poorly characterized. In this study, we have designed an in vitro model of hemorrhagic stroke in order to investigate conditions that promote the oxidation of bilirubin to form vasoactive compounds. Using our model, we created a basic hematoma system of blood, CSF, and hemeoxygenase-1. We manipulated this system in various ways, incubated it and determined the concentration of vasoactive bilirubin oxidation products that resulted. Conditions where cytochrome oxidase was stimulated caused an increase bilirubin oxidation products (292.6 +/- 39.9 mu mol/L respectively, vs. 79.3 +/- 1.3 mu mol/L for the basic reaction, p < 0.05), which was attenuated by cyanide. Our data suggest that bilirubin oxidation products may be produced by oxidation(s) requiring an oxygen-utilizing enzyme like cytochrome oxidase.