Oxidative stress induced necroptosis activation is involved in the pathogenesis of hyperoxic acute lung injury
Oxidative stress induced necroptosis activation is involved in the pathogenesis of hyperoxic acute lung injury
复制标题
氧化应激诱导的坏死性凋亡激活参与高氧急性肺损伤的发病机制
DOI：
10.1016/j.bbrc.2017.12.100
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发表时间：
2018-01-15
影响因子：
3.1
通讯作者：
Liu, W. W.
中科院分区：
文献类型：
--
作者：
Han, C. H.;Guan, Z. B.;Liu, W. W.
坏死性凋亡已被发现参与了一些肺部疾病的发病机制，但其在高氧急性肺损伤（HALI）中的作用尚不清楚。本研究旨在探讨坏死性凋亡在高压高氧致大鼠HALI发病机制中的作用。将大鼠分为对照组、HALT组、坏死凋亡抑制剂Nec-1组和依达拉奉组。将大鼠暴露于250 kPa的纯氧中6 h，以诱导HALI。在高氧暴露前30 min，腹腔注射Nec-1或依达拉奉，在高氧暴露后24 h处死大鼠。通过组织学、肺水干比（WAD）和支气管肺泡灌洗液（BALF）生化指标评价肺损伤;测定血清和血浆氧化应激水平、RIP 1、RIP 3和MLKL的表达以及RIP 1和RIP 3之间的相互作用。结果表明，高氧暴露可引起肺组织损伤，肺组织坏死细胞增多，RIP 1、RIP 3和MLKL表达增加。依达拉奉预处理不仅能抑制HALI的氧化应激，还能减少坏死细胞，降低RIP 1、RIP 3和MLKL的表达，改善肺病理。Nec-1预处理抑制坏死性凋亡，改善肺病理，但对氧化应激影响不大。本研究提示高氧暴露诱导的氧化应激可能激活坏死性凋亡，参与HALI的病理过程，针对坏死性凋亡的治疗策略可能成为HALL的有效治疗手段。(C)2017由Elsevier Inc.出版
Necroptosis has been found to be involved in the pathogenesis of some lung diseases, but its role in hyperoxic acute lung injury (HALI) is still unclear. This study aimed to investigate contribution of necroptosis to the pathogenesis of HALI induced by hyperbaric hyperoxia exposure in a rat model. Rats were divided into control group, HALT group, Nec-1 (necroptosis inhibitor) group and edaravone group. Rats were exposed to pure oxygen at 250 kPa for 6 h to induce HALI. At 30 min before hyperoxia exposure, rats were intraperitoneally injected with Nec-1 or edaravone, and sacrificed at 24 h after hyperoxia exposure. Lung injury was evaluated by histology, lung water to dry ratio (WAD) and bronchoalveolar lavage fluid (BALF) biochemistry; the serum and plasma oxidative stress, expression of RIP1, RIP3 and MLKL, and interaction between RIP1 and RIP3 were determined. Results showed hyperoxia exposure significantly caused damage to lung and increased necroptotic cells and the expression of RIP1, RIP3 and MLKL. Edaravone pre-treatment not only inhibited the oxidative stress in HALI, but also reduced necroptotic cells, decreased the expression of RIP1, RIP3 and MLKL and improved lung pathology. Nec-1 pretreatment inhibited necroptosis and improved lung pathology, but had little influence on oxidative stress. This study suggests hyperoxia exposure induces oxidative stress may activate necroptosis, involving in the pathology of HALI, and strategies targeting necroptosis may become promising treatments for HALL. (C) 2017 Published by Elsevier Inc.