Utepbergenov D I, Mertsch K, Sporbert A, Tenz K, Paul M, Haseloff R F, Blasig I E
Institute of Chemical Kinetics and Combustion, Novosibirsk, Russia.
FEBS Lett. 1998 Mar 13;424(3):197-201. doi: 10.1016/s0014-5793(98)00173-2.
A cell culture model of blood-brain barrier (BBB, coculture of rat brain endothelial cells with rat astrocytes) was used to investigate the effect of nitric oxide (.NO) on the damage of the BBB induced by hypoxia/reoxygenation (H/R). Permeability coefficient of fluorescein across the endothelium was used as a marker of BBB tightness. The permeability coefficient increased 5.2 times after H/R indicating strong disruption of the BBB. The presence of the .NO donor S-nitroso-N-acetylpenicillamine (SNAP, 30 microM), authentic .NO (6 microM) or superoxide dismutase (50 units/ml) during H/R attenuated H/R-induced increase in permeability. 30 microM SNAP or 6 microM .NO did not influence the function of BBB during normoxia, however, severe disruption was observed using 150 microM of SNAP and more than 24 microM of .NO. After H/R of endothelial cells, the content of malondialdehyde (MDA) increased 2.3 times indicating radical-induced peroxidation of membrane lipids. 30 microM SNAP or 6 microM authentic .NO completely prevented MDA formation. The results show that .NO may effectively scavenge reactive oxygen species formed during H/R of brain capillary endothelial cells, affording protection of BBB at the molecular and functional level.
采用血脑屏障细胞培养模型（血脑屏障，大鼠脑内皮细胞与大鼠星形胶质细胞共培养）研究一氧化氮（·NO）对缺氧/复氧（H/R）诱导的血脑屏障损伤的影响。以荧光素跨内皮的通透系数作为血脑屏障紧密性的标志物。H/R后通透系数增加了5.2倍，表明血脑屏障受到严重破坏。在H/R期间存在·NO供体S-亚硝基-N-乙酰青霉胺（SNAP，30 μM）、纯·NO（6 μM）或超氧化物歧化酶（50单位/ml）可减轻H/R诱导的通透性增加。30 μM SNAP或6 μM·NO在常氧期间不影响血脑屏障的功能，然而，使用150 μM SNAP和超过24 μM·NO时观察到严重破坏。内皮细胞H/R后，丙二醛（MDA）含量增加了2.3倍，表明自由基诱导的膜脂质过氧化。30 μM SNAP或6 μM纯·NO完全阻止了MDA的形成。结果表明，·NO可有效清除脑毛细血管内皮细胞H/R期间形成的活性氧，在分子和功能水平上保护血脑屏障。
