N-acetylcysteine attenuates reactive-oxygen-species-mediated endoplasmic reticulum stress during liver ischemia-reperfusion injury
N-acetylcysteine attenuates reactive-oxygen-species-mediated endoplasmic reticulum stress during liver ischemia-reperfusion injury
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DOI：
10.3748/wjg.v20.i41.15289
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发表时间：
2014-11-07
影响因子：
4.3
通讯作者：
Rao, Jian-Hua
中科院分区：
文献类型：
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作者：
Sun, Yong;Pu, Li-Yong;Rao, Jian-Hua
目的：探讨N-乙酰半胱氨酸(NAC)对肝脏缺血再灌注损伤(IRI)时内质网(ER)应激和组织损伤的影响。方法：小鼠于缺血前2 h腹腔注射NAC(300 mg/kg)。实时定量聚合酶链式反应和Western blotting检测内质网应激分子(GRP78、ATF4和CHOP)。为探讨NAC在活性氧(ROS)介导的内质网应激和细胞凋亡中的作用，检测了过氧化氢(H_2O_2)和山茶素(TG)对培养肝细胞乳酸脱氢酶(LDH)的影响。结果：从谷胱甘肽、丙二醛、血清丙氨酸氨基转移酶(ALT)水平和组织病理学角度来看，NAC可显著降低ROS水平，减轻ROS诱导的肝损伤。在NAC处理的小鼠中，ROS介导的内质网应激显著受到抑制。此外，NAC可显著降低再灌流后caspase-3活性和细胞凋亡率，并与Bcl2和Bclxl蛋白表达相关。结论：NAC对肝细胞在IRI中的保护作用提供了新的证据。NAC通过抑制ROS介导的内质网应激，可能在抑制内质网应激相关的细胞凋亡途径中起关键作用。(C)2014百仕登出版集团有限公司，版权所有。
AIM: To investigate the effects of N-acetylcysteine (NAC) on endoplasmic reticulum (ER) stress and tissue injury during liver ischemia reperfusion injury (IRI).METHODS: Mice were injected with NAC (300 mg/kg) intraperitoneally 2 h before ischemia. Real-time polymerase chain reaction and western blotting determined ER stress molecules (GRP78, ATF4 and CHOP). To analyze the role of NAC in reactive oxygen species (ROS)-mediated ER stress and apoptosis, lactate dehydrogenase (LDH) was examined in cultured hepatocytes treated by H2O2 or thapsigargin (TG).RESULTS: NAC treatment significantly reduced the level of ROS and attenuated ROS-induced liver injury after IRI, based on glutathione, malondialdehyde, serum alanine aminotransferase levels, and histopathology. ROS-mediated ER stress was significantly inhibited in NAC-treated mice. In addition, NAC treatment significantly reduced caspase-3 activity and apoptosis after reperfusion, which correlated with the protein expression of Bcl-2 and Bcl-xl. Similarly, NAC treatment significantly inhibited LDH release from hepatocytes treated by H2O2 or TG.CONCLUSION: This study provides new evidence for the protective effects of NAC treatment on hepatocytes during IRI. Through inhibition of ROS-mediated ER stress, NAC may be critical to inhibit the ER-stress-related apoptosis pathway. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.