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首页> 外文期刊>Medical Gas Research >Normobaric hyperoxia protects the blood brain barrier through inhibiting Nox2 containing NADPH oxidase in ischemic stroke
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Normobaric hyperoxia protects the blood brain barrier through inhibiting Nox2 containing NADPH oxidase in ischemic stroke

机译：常压高氧通过抑制缺血性中风中含有Nox2的NADPH氧化酶来保护血脑屏障

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Normobaric hyperoxia (NBO) has been shown to be neuro- and vaso-protective during ischemic stroke. However, the underlying mechanisms remain to be fully elucidated. Activation of NADPH oxidase critically contributes to ischemic brain damage via increase in ROS production. We herein tested the hypothesis that NBO protects the blood-brain barrier (BBB) via inhibiting gp91phox (or called Nox2) containing NADPH oxidase in a mouse model of middle cerebral artery occlusion (MCAO). Wild-type C57/BL6 mice and gp91phoxknockout mice were given NBO (95% O2) or normoxia (21% O2) during 90-min MCAO, followed by 22.5 hrs of reperfusion. BBB damage was quantified by measuring Evans blue extravasation. The protein levels of matrix metalloproteinase-9 (MMP-9), tight junction protein occludin and gp91phox were assessed with western blot. Gel zymography was used to assess the gelatinolytic activity of MMP-9. In the wild type mice, cerebral ischemia and reperfusion led to remarkable Evans blue extravasation, significantly increased gp91phox and MMP-9 levels and decreased occludin levels in the ischemic brain tissue. In gp91phox knockout mice, the changes in Evans blue extravasation, MMP-9 and occludin were at much smaller magnitudes when compared to the wild type. Importantly, NBO treatment significantly reduced the changes in all measured parameters in wild type mice, while did not cause additional reductions in these changes when gp91phox was knocked out. These results indicate that activation of Nox2 containing NADPH oxidase is implicated in the induction of MMP-9, loss of occludin and BBB disruption in ischemic stroke, and inhibition of Nox2 may be an important mechanism underlying NBO-afforded BBB protection.
机译：正常高氧血症（NBO）已显示在缺血性中风期间具有神经和血管保护作用。但是，其潜在机制仍有待充分阐明。 NADPH氧化酶的激活通过增加ROS的产生对缺血性脑损伤至关重要。我们在本文中测试了NBO通过抑制中脑动脉闭塞（MCAO）小鼠模型中含有NADPH氧化酶的gp91 phox （或称为Nox2）来保护血脑屏障（BBB）的假设。对野生型C57 / BL6小鼠和gp91 phox 敲除小鼠给予NBO（95％O 2 ）或常氧（21％O 2 ）在90分钟的MCAO中，然后进行22.5小时的再灌注。通过测量伊文思蓝外渗来量化BBB损伤。用western blot检测基质金属蛋白酶9（MMP-9），紧密连接蛋白occludin和gp91 phox 的蛋白水平。凝胶酶谱法用于评估MMP-9的明胶分解活性。在野生型小鼠中，脑缺血和再灌注导致明显的伊文思蓝外渗，显着增加缺血性脑组织中gp91 ho> 和MMP-9的水平，降低闭合蛋白的水平。与野生型相比，在gp91 phox 敲除小鼠中，Evans蓝色外渗，MMP-9和occludin的变化幅度要小得多。重要的是，当敲除gp91 phox 时，NBO处理显着降低了野生型小鼠中所有测得参数的变化，而没有引起这些变化的进一步降低。这些结果表明，含有NADPH氧化酶的Nox2的激活与缺血性卒中中MMP-9的诱导，闭合蛋白的丢失和BBB的破坏有关，而Nox2的抑制可能是NBO负担得起的BBB保护的重要机制。

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