Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Free Radic Biol Med. 2011 Jun 15;50(12):1780-6. doi: 10.1016/j.freeradbiomed.2011.03.028. Epub 2011 Mar 31.
Interrupted reperfusion reduces ischemia/reperfusion (I/R) injury. This study was designed to determine whether NADPH oxidase participates in the neural protection against global I/R injury after interrupted reperfusion. Mice were randomly divided into five groups: sham (sham-operated), I/R (20-min global I/R), RR (I/R+interrupted reperfusion), Apo (I/R+apocynin administration), and RR+Apo. Behavioral tests (pole test, beam walking, and Morris water maze) and Nissl staining were undertaken in all five groups; superoxide levels, expression of gp91(phox) and p47(phox), p47(phox) translocation, and Rac1 activation were measured in the sham, I/R, and RR groups. The motor coordination, bradykinesia, and spatial learning and memory, as well as the neuron survival rates, were better in the RR, Apo, and RR+Apo groups than in the I/R group. The NADPH oxidase-dependent superoxide levels, p47(phox) and gp91(phox) expression, p47(phox) translocation, and Rac1 activation were lower in the RR group than in the I/R group. In conclusion, the neural protective effect of interrupted reperfusion is at least partly mediated by decreasing the expression and assembly of NADPH oxidase and the levels of NADPH oxidase-derived superoxide. The most striking reduction Rac1-GTP in the RR group suggests that interrupted reperfusion also acts on the activation of assembled NADPH oxidase by reducing the availability of Rac1-GTP.
再灌注中断可减轻缺血/再灌注（I/R）损伤。本研究旨在确定烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶是否参与再灌注中断后的全脑 I/R 损伤的神经保护作用。小鼠随机分为 5 组：假手术（sham）组、I/R 组（20 分钟全脑 I/R）、RR 组（I/R+再灌注中断）、Apo 组（I/R+apocynin 给药）和 RR+Apo 组。所有 5 组均进行行为学测试（棒测试、走棒测试和 Morris 水迷宫）和尼氏染色；在 sham、I/R 和 RR 组中测量超氧阴离子水平、gp91（phox）和 p47（phox）的表达、p47（phox）易位和 Rac1 激活。与 I/R 组相比，RR、Apo 和 RR+Apo 组的运动协调、运动迟缓以及空间学习和记忆能力更好，神经元存活率更高。RR 组 NADPH 氧化酶依赖性超氧阴离子水平、p47（phox）和 gp91（phox）表达、p47（phox）易位和 Rac1 激活均低于 I/R 组。结论：再灌注中断的神经保护作用至少部分是通过降低 NADPH 氧化酶的表达和组装以及 NADPH 氧化酶衍生的超氧阴离子水平来实现的。RR 组 Rac1-GTP 水平降低最为明显，提示再灌注中断还通过降低 Rac1-GTP 的可用性来作用于组装的 NADPH 氧化酶的激活。
