In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats
In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats
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DOI：
10.1038/sj.bjp.0705138
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发表时间：
2003-03-01
影响因子：
7.3
通讯作者：
Bulbena, O
中科院分区：
文献类型：
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作者：
Serrano-Mollar, A;Closa, D;Bulbena, O
(1)巴塞罗那生物医学研究所医学生物分析系(IIBB-IDIBAPS)，西班牙巴塞罗那CSIC；(2)西班牙贝拉特拉自治大学兽医学院动物病理学系；(3)西班牙巴伦西亚巴伦西亚大学医学院药理学系和(4)巴伦西亚大学医学院生理学系1本研究检测抗氧化剂N-乙酰半胱氨酸对博莱霉素诱导的大鼠肺纤维化的活性，重点放在早期炎症阶段2，给予N-乙酰半胱氨酸(300 mg kg(-1)天(-1)，腹腔注射)的大鼠肺湿重增加较少，蛋白质、乳酸脱氢酶、肺泡灌洗液中中性粒细胞和巨噬细胞计数及肺组织髓过氧化物酶活性在博莱霉素治疗后3天明显改善。3博莱霉素治疗3天后肺组织GSH/GSSG比值降低，脂质过氧化氢含量增加。这些变化可被N-乙酰半胱氨酸减弱。博莱霉素暴露的大鼠肺泡巨噬细胞释放出大量的超氧阴离子和一氧化氮。4.N-乙酰半胱氨酸抑制博莱霉素诱导的肺组织核因子-kappaB(位移分析和免疫组织化学)活化，降低早期炎症细胞因子、肿瘤坏死因子-α、白介素β、白介素6和巨噬细胞炎性蛋白-2在博莱霉素染毒后第1天和第3天的升高水平。5在博莱霉素后第15天，N-乙酰半胱氨酸减少博莱霉素染毒大鼠肺组织中胶原的沉积(羟基脯氨酸含量分别为6351+/669和4626+/288/肺)；
(1)Department of Medical Bioanalysis, Instituto de Investigaciones Biomedicas de Barcelona (IIBB-IDIBAPS), CSIC, Barcelona, Spain; (2)Department of Animal Pathology, Veterinary School, Universitat Autonoma de Barcelona, Bellaterra, Spain; (3)Pharmacology Department, Faculty of Medicine, Universitat de Valencia, Valencia, Spain and (4)Physiology Department, Faculty of Medicine, Universitat de Valencia, Valencia, Spain1 This study examines the activity of the antioxidant N-acetylcysteine on bleomycin-induced pulmonary fibrosis in rats with emphasis on the early inflammatory phase.2, Rats receiving N-acetylcysteine (300 mg kg(-1) day(-1), intraperitoneal) had less augmented lung wet weight, and lower levels of proteins, lactate dehydrogenase, neutrophil and macrophage counts in bronchoalveolar lavage fluid and lung myeloperoxidase activity with a betterment of histological score at 3 days postbleomycin.3 A diminished lung GSH/GSSG ratio and augmented lipid hydroperoxides were observed 3 days postbleomycin. These changes were attenuated by N-acetylcysteine. Alveolar macrophages from bleomycin-exposed rats released augmented amounts of superoxide anion and nitric oxide. N-Acetylcysteine did not modify superoxide anion generation but reduced the increased production of nitric oxide.4 N-Acetylcysteine suppressed the bleomycin-induced increased activation of lung NF-kappaB (shift assay and immunohistochemistry), and decreased the augmented levels of the early inflammatory cytokines, tumour necrosis factor-alpha, interleukin-beta, interleukin-6 and macrophage inflammatory protein-2 observed in bronchoalveolar lavage fluid at I and 3 days postbleomycin exposure.5 At 15 days postbleomycin, N-acetylcysteine decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content: 6351+/-669 and 4626+/-288 mug per lung in drug vehicle- and Nacetylcysteine-treated rats, respectively; P