Mata M, Ruíz A, Cerdá M, Martinez-Losa M, Cortijo J, Santangelo F, Serrano-Mollar A, Llombart-Bosch A, Morcillo E J
Dept of Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain.
Eur Respir J. 2003 Dec;22(6):900-5. doi: 10.1183/09031936.03.00018003.
Oxidative stress is involved in the pathogenesis of pulmonary fibrosis, therefore antioxidants may be of therapeutic value. Clinical work indicates that N-acetylcysteine (NAC) may be beneficial in this disease. The activity of this antioxidant was examined on bleomycin-induced lung damage, mucus secretory cells hyperplasia and mucin Muc5ac gene expression in rats. NAC (3 mmol x kg(-1) x day(-1)) or saline was given orally to Sprague-Dawley rats for 1 week prior to a single intratracheal instillation of bleomycin (2.5 U x kg(-1)) and for 14 days postinstillation. NAC decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,257+/-323 and 3,200+/-192 microg x lung(-1) in vehicle- and NAC-treated rats, respectively) and lessened the fibrotic area assessed by morphometric analysis. The bleomycin-induced increases in lung tumour necrosis factor-alpha and myeloperoxidase activity were reduced by NAC treatment. The numbers of mucus secretory cells in airway epithelium, and the Muc5ac messenger ribonucleic acid and protein expression, were markedly augmented in rats exposed to bleomycin. These changes were significantly reduced in NAC-treated rats. These results indicate that bleomycin increases the number of airway secretory cells and their mucin production, and that oral N-acetylcysteine improved pulmonary lesions and reduced the mucus hypersecretion in the bleomycin rat model.
氧化应激参与了肺纤维化的发病机制，因此抗氧化剂可能具有治疗价值。临床研究表明，N-乙酰半胱氨酸（NAC）可能对这种疾病有益。本研究检测了该抗氧化剂对博来霉素诱导的大鼠肺损伤、黏液分泌细胞增生及黏蛋白Muc5ac基因表达的影响。在单次气管内注入博来霉素（2.5 U·kg-1）前1周及注入后14天，给Sprague-Dawley大鼠口服NAC（3 mmol·kg-1·d-1）或生理盐水。NAC可减少博来霉素处理大鼠的胶原蛋白沉积（分别给予赋形剂和NAC处理的大鼠肺组织羟脯氨酸含量为4,257±323和3,200±192 μg·肺-1），并通过形态学分析减少纤维化面积。NAC处理可降低博来霉素诱导的肺肿瘤坏死因子-α和髓过氧化物酶活性升高。博来霉素处理的大鼠气道上皮黏液分泌细胞数量、Muc5ac信使核糖核酸和蛋白表达均显著增加。NAC处理的大鼠上述变化明显减少。这些结果表明，博来霉素可增加气道分泌细胞数量及其黏蛋白产生，口服N-乙酰半胱氨酸可改善博来霉素大鼠模型的肺部病变并减少黏液分泌过多。
