Moore S A, Figard P H, Spector A A, Hart M N
Department of Pathology, University of Iowa, Iowa City 52240.
J Neurochem. 1989 Aug;53(2):376-82. doi: 10.1111/j.1471-4159.1989.tb07345.x.
Cerebral microvessels isolated from perfused, adult murine brain produce a compound with the chromatographic properties of a monohydroxyeicosatetraenoic acid when incubated with arachidonic acid or stimulated with calcium ionophore A23187. The formation of this arachidonic acid metabolite is not reduced in the presence of the cyclooxygenase inhibitor ibuprofen, but it is abolished by the lipoxygenase inhibitor nordihydroguaiaretic acid. Analysis by gas chromatography combined with chemical ionization and electron impact mass spectrometry of reduced and nonreduced derivatives of the metabolite, indicate that the compound is 12-hydroxyeicosatetraenoic acid. Fractions of isolated microvessels enriched with capillaries produce 2.1 times more 12-hydroxyeicosatetraenoic acid per microgram of protein than do fractions of microvessels enriched with arterioles. These studies confirm that brain microvessels can produce 12-hydroxyeicosatetraenoic acid and strongly suggest that cerebral endothelia are the primary source of microvessel-derived 12-hydroxyeicosatetraenoic acid. They further suggest that in brain injury, the liberation and accumulation of arachidonic acid in cerebral tissues may lead to the production of 12-hydroxyeicosatetraenoic acid within microvessels. The 12-hydroxyeicosatetraenoic acid formed in this way may mediate some of the blood-brain barrier and cerebrovascular dysfunction that occurs following stroke, brain trauma, or seizures.
从灌注的成年小鼠大脑中分离出的脑微血管，在与花生四烯酸一起孵育或用钙离子载体A23187刺激时，会产生一种具有单羟基二十碳四烯酸色谱特性的化合物。这种花生四烯酸代谢产物的形成在环氧化酶抑制剂布洛芬存在的情况下不会减少，但会被脂氧合酶抑制剂去甲二氢愈创木酸消除。通过气相色谱结合化学电离和电子轰击质谱对该代谢产物的还原和非还原衍生物进行分析，表明该化合物是12-羟基二十碳四烯酸。富含毛细血管的分离微血管部分每微克蛋白质产生的12-羟基二十碳四烯酸比富含小动脉的微血管部分多2.1倍。这些研究证实脑微血管可以产生12-羟基二十碳四烯酸，并强烈表明脑内皮细胞是微血管衍生的12-羟基二十碳四烯酸的主要来源。它们进一步表明，在脑损伤中，脑组织中花生四烯酸的释放和积累可能导致微血管内产生12-羟基二十碳四烯酸。以这种方式形成的12-羟基二十碳四烯酸可能介导中风、脑外伤或癫痫发作后发生的一些血脑屏障和脑血管功能障碍。
