Interrupted reperfusion reduces the activation of NADPH oxidase after cerebral I/R injury
Interrupted reperfusion reduces the activation of NADPH oxidase after cerebral I/R injury
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DOI：
10.1016/j.freeradbiomed.2011.03.028
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发表时间：
2011-06-15
影响因子：
7.4
通讯作者：
Xia, Qiang
中科院分区：
文献类型：
--
作者：
Shen, Jia;Bai, Xiao-Yin;Xia, Qiang
中断再灌注可减少缺血/再灌注 (I/R) 损伤。本研究旨在确定 NADPH 氧化酶是否参与中断再灌注后针对整体 I/R 损伤的神经保护。将小鼠随机分为五组：假手术（假手术）、I/R（20 分钟整体 I/R）、RR（I/R + 中断再灌注）、Apo（I/R + 夹竹桃麻素给药）和 RR + Apo。所有五组均进行行为测试（杆测试、平衡木行走和莫里斯水迷宫）和尼氏染色；在假手术组、I/R 组和 RR 组中测量超氧化物水平、gp91(phox) 和 p47(phox) 表达、p47(phox) 易位和 Rac1 激活。 RR 的运动协调性、运动迟缓、空间学习和记忆以及神经元存活率更好。 Apo 和 RR + Apo 组高于 I/R 组。 RR 组中 NADPH 氧化酶依赖性超氧化物水平、p47(phox) 和 gp91(phox) 表达、p47(phox) 易位和 Rac1 激活均低于 I/R 组。总之，中断再灌注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 氧化酶衍生的超氧化物的水平来介导的。 RR 组中 Rac1-GTP 最显着的减少表明，中断再灌注还可以通过减少 Rac1-GTP 的可用性来激活组装的 NADPH 氧化酶。 (C) 2011 Elsevier Inc. 保留所有权利。
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. (C) 2011 Elsevier Inc. All rights reserved.