Topaloğlu Nurhayat, Olgun Yıldızeli Şehnaz, Şener Göksel, Laçin Tunç, Şehirli Özer, Bozkurtlar Emine, Çelikel Çiğdem, Ceyhan Berrin
Department of Chest Diseases, Bolu State Hospital, Bolu, Turkey.
Chest Diseases and Intensive Care Medicine Department, Medicine Faculty of Marmara University, İstanbul, Turkey.
Turk Gogus Kalp Damar Cerrahisi Derg. 2018 Sep 16;26(4):588-597. doi: 10.5606/tgkdc.dergisi.2019.15149. eCollection 2018 Oct.
This study aims to investigate the early- and late-term effects of pharmacological inhibition of cysteinyl leukotriene activity by using montelukast in bleomycin-induced inflammatory and oxidative lung injury in an animal model.
The study included 48 male Wistar albino rats (weighing 250 g to 300 g). Rats were administered intratracheal bleomycin or saline and assigned into groups to receive montelukast or saline. Bronchoalveolar lavage fluid and lung tissue samples were collected four and 15 days after bleomycin administration.
Bleomycin resulted in significant increases in tumor necrosis factor-alpha levels (4.0±1.4 pg/mL in controls vs. 44.1±14.5 pg/mL in early-term vs. 30.3±5.7 pg/mL in late-term, p<0.001 and p<0.001, respectively), transforming growth factor beta 1 levels (28.6±6.6 pg/mL vs. 82.3±14.1 pg/mL in early-term vs. 60.1±2.9 pg/mL in late-term, p<0.001 and p<0.001, respectively), and fibrosis score (1.85±0.89 in early-term vs. 5.60±1.14 in late-term, p<0.001 and p<0.01, respectively). In bleomycin exposed rats, collagen content increased only in the late-term (15.3±3.0 ?g/mg in controls vs. 29.6±9.1 ?g/mg in late-term, p<0.001). Montelukast treatment reversed all these biochemical indices as well as histopathological alterations induced by bleomycin.
Montelukast attenuates bleomycin-induced inflammatory and oxidative lung injury and prevents lung collagen deposition and fibrotic response. Thus, cysteinyl leukotriene receptor antagonists might be regarded as new therapeutic agents for idiopathic pulmonary fibrosis.
本研究旨在通过在博来霉素诱导的动物模型肺炎症和氧化损伤中使用孟鲁司特，探讨药理学抑制半胱氨酰白三烯活性的早期和晚期效果。
本研究纳入48只雄性Wistar白化大鼠（体重250克至300克）。大鼠经气管内给予博来霉素或生理盐水，并分组接受孟鲁司特或生理盐水。在给予博来霉素后第4天和第15天收集支气管肺泡灌洗液和肺组织样本。
博来霉素导致肿瘤坏死因子-α水平显著升高（对照组为4.0±1.4皮克/毫升，早期为44.1±14.5皮克/毫升，晚期为30.3±5.7皮克/毫升，p分别<0.001和<0.001），转化生长因子β1水平显著升高（28.6±6.6皮克/毫升，早期为82.3±14.1皮克/毫升，晚期为60.1±2.9皮克/毫升，p分别<0.001和<0.001），以及纤维化评分显著升高（早期为1.85±0.89，晚期为5.60±1.14，p分别<0.001和<0.01）。在博来霉素暴露的大鼠中，胶原蛋白含量仅在晚期增加（对照组为15.3±3.0微克/毫克，晚期为29.6±9.1微克/毫克，p<0.001）。孟鲁司特治疗逆转了所有这些生化指标以及博来霉素诱导的组织病理学改变。
孟鲁司特减轻博来霉素诱导的炎症和氧化肺损伤，并防止肺胶原蛋白沉积和纤维化反应。因此，半胱氨酰白三烯受体拮抗剂可能被视为特发性肺纤维化的新治疗药物。
