Department ofNeurology, University Hospital, Goethe-University Frankfurt, Frankfurt/Main, Germany.
Neurobiol Dis. 2010 Oct;40(1):185-92. doi: 10.1016/j.nbd.2010.05.023. Epub 2010 May 23.
Reactive oxygen species (ROS) are mediators of brain injury in ischemia/reperfusion. An involvement of the NADPH oxidase Nox2 has been demonstrated. In contrast, only little is known about the contribution of the Nox1 homologue in this context. Thus, we studied the role of Nox1 in early cerebral reperfusion injury in the middle cerebral artery filament occlusion model using Nox1 knockout mice. Genetic deletion of a functional Nox1 lead to a 55% attenuation in lesion size at 24h after induction of 1h ischemia (p<0.05). This result was paralleled by a significant improvement of neurological outcome, preservation of blood-brain barrier integrity and reduced cerebral edema in Nox1(y/)(-) compared to WT mice. Interestingly, no difference in infarct size between WT and Nox1(y/)(-) was observed with an occlusion time of 2h and longer. Apoptosis rate as measured by TUNEL staining was similar between the groups. Moreover, infusion of the antioxidant TEMPOL as well as of the unspecific NO-synthase inhibitor l-NAME elicited similar changes with respect to ischemic tissue damage between WT and Nox1-deficient mice. In conclusion, Nox1 is involved in the pathophysiology of cerebral ischemia. Our data however indicate that ROS-mediated direct cellular injury is unlikely to explain the protective effect achieved by genetic deletion of the enzyme.
活性氧（ROS）是脑缺血/再灌注损伤的介质。已经证明 NADPH 氧化酶 Nox2 的参与。相比之下，在这种情况下，对于 Nox1 同源物的贡献知之甚少。因此，我们使用 Nox1 敲除小鼠研究了 Nox1 在大脑中动脉纤维闭塞模型中的早期再灌注损伤中的作用。诱导 1 小时缺血后 24 小时，功能 Nox1 的基因缺失导致病变大小减少 55%（p<0.05）。与 WT 小鼠相比，Nox1(y/)(-) 的神经功能结局显著改善、血脑屏障完整性得以保留且脑水肿减少，这一结果与神经功能结局相平行。有趣的是，在闭塞时间为 2 小时及更长时间时，WT 和 Nox1(y/)(-) 之间的梗塞面积没有差异。TUNEL 染色测量的细胞凋亡率在两组之间相似。此外，抗氧化剂 TEMPOL 的输注以及非特异性 NO 合酶抑制剂 l-NAME 的输注在 WT 和 Nox1 缺陷型小鼠之间对缺血性组织损伤产生了类似的变化。总之，Nox1 参与了脑缺血的病理生理学。然而，我们的数据表明，ROS 介导的直接细胞损伤不太可能解释通过基因缺失酶实现的保护作用。
