Oxidative damage to nucleic acids in severe emphysema.
Oxidative damage to nucleic acids in severe emphysema.
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DOI：
10.1378/chest.08-2257
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发表时间：
2009-04
期刊：
影响因子：
9.6
通讯作者：
Pierce RA
中科院分区：
文献类型：
--
作者：
Deslee G;Woods JC;Moore C;Conradi SH;Gierada DS;Atkinson JJ;Battaile JT;Liu L;Patterson GA;Adair-Kirk TL;Holtzman MJ;Pierce RA
氧化应激是肺气肿发病的关键因素，但核酸的氧化在很大程度上被忽视了。本研究的目的是探讨严重肺气肿肺组织中核酸的氧化损伤。取自肺移植患者的13个人重度肺气肿肺，其中5个为α-1抗胰蛋白酶缺乏症。对照肺组织取自非COPD肺(n=8)和供体肺(n=8)。用免疫组织化学方法研究DNA和RNA的氧化。同时进行形态计量学(平均线形截距[LM]和CT扫描)及CD68和中性粒细胞弹性蛋白酶免疫组织化学染色。肺气肿患者肺泡壁细胞的核酸氧化程度高于非COPD患者和供者肺(p<；0.01)。在肺气肿肺中，通过组织学(光镜)和CT扫描(<；−950Hounsfield单位；p<；0.05)评估的更严重的肺气肿区域，肺泡壁细胞中的核酸氧化损伤增加。与典型肺气肿相比，AATD肺中巨噬细胞(p<；0.05)和呼吸道上皮细胞(p<；0.01)的核酸氧化水平更高。用DNase和RNase处理的肺泡壁细胞中，RNA氧化比DNA氧化更为普遍。我们首次证明了核酸，特别是RNA，在人类肺气肿的肺中被氧化。肺泡壁细胞核酸氧化损伤水平与肺气肿严重程度之间的相关性提示在肺气肿的发病机制中具有潜在的作用。
Oxidative stress is a key element in the pathogenesis of emphysema, but oxidation of nucleic acids has been largely overlooked. The aim of this study was to investigate oxidative damage to nucleic acids in severe emphysematous lungs. Thirteen human severe emphysematous lungs, including five with α1-antitrypsin deficiency (AATD), were obtained from patients receiving lung transplantation. Control lung tissue was obtained from non-COPD lungs (n = 8) and donor lungs (n = 8). DNA and RNA oxidation were investigated by immunochemistry. Morphometry (mean linear intercept [Lm] and CT scan) and immunostaining for CD68 and neutrophil elastase also were performed. Nucleic acid oxidation was increased in alveolar wall cells in emphysematous lungs compared to non-COPD and donor lungs (p < 0.01). In emphysematous lungs, oxidative damage to nucleic acids in alveolar wall cells was increased in the more severe emphysematous areas assessed by histology (Lm, > 0.5 mm; p < 0.05) and CT scan (< −950 Hounsfield units; p < 0.05). Compared to classic emphysema, AATD lungs exhibited higher levels of nucleic acid oxidation in macrophages (p < 0.05) and airway epithelial cells (p < 0.01). Pretreatments with DNase and RNase demonstrated that RNA oxidation was more prevalent than DNA oxidation in alveolar wall cells. We demonstrated for the first time that nucleic acids, especially RNA, are oxidized in human emphysematous lungs. The correlation between the levels of oxidative damage to nucleic acids in alveolar wall cells and the severity of emphysema suggest a potential role in the pathogenesis of emphysema.
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单一与反复的香烟烟雾暴露后，支气管趋化因子表达不同。
影响因子：
5.8
作者：
Betsuyaku, Tomoko;Hamamura, Ichiro;Hata, Junko;Takahashi, Hiroshi;Mitsuhashi, Hiroaki;Adair-Kirk, Tracy L.;Senior, Robert M.;Nishimura, Masaharu
通讯作者：
Nishimura, Masaharu
影响因子：
6.1
作者：
Nunomura, A;Chiba, S;Perry, G
通讯作者：
Perry, G
影响因子：
1.7
作者：
Nunomura, A;Chiba, S;Perry, G
通讯作者：
Perry, G
影响因子：
9.6
作者：
Mulgrew, AT;Taggart, CC;McElvaney, NG
通讯作者：
McElvaney, NG
DOI：
10.1111/j.1365-2362.2004.01343.x
发表时间：
2004-05-01
影响因子：
5.5
作者：
Martinet, W;De Meyer, GRY;Kockx, MM
通讯作者：
Kockx, MM