Langenbach Shenna Y, Wheaton Ben J, Fernandes Darren J, Jones Catherine, Sutherland Tara E, Wraith Bronwyn C, Harris Trudi, Schuliga Michael J, McLean Catriona, Stewart Alastair G
Department of Pharmacology, University of Melbourne, Melbourne, Victoria, Australia.
Can J Physiol Pharmacol. 2007 Jul;85(7):727-38. doi: 10.1139/Y07-065.
Bleomycin-induced lung fibrosis in mice reproduces some key features of pulmonary fibrosis in humans including alveolar inflammation, myofibroblast proliferation, and collagen deposition. Glucocorticoids have been used as first-line therapy for the treatment of lung fibrosis, although their clinical efficacy is equivocal. We examined the effect of the glucocorticoid, methylprednisolone (MP), and the estrogen metabolite, 2-methoxyestradiol (2MEO) on bleomycin-induced bronchoalveolar inflammation, fibrosis, and changes in lung function. The characterization of the time-course of the bleomycin-induced fibrosis indicated that lung dry mass and hydroxyproline content showed less variance than histopathological assessment of fibrosis. The bleomycin-induced increases in bronchoalveolar lavage (BAL) fluid cell number and protein levels were not significantly influenced by treatment with either MP (1 mg.(kg body mass)(-1).day(-1), i.p.) or 2MEO (50 mg.(kg body mass)(-1).day(-1), i.p.). Lung fibrosis, measured histopathologically or by hydroxyproline content, was not significantly influenced by either MP or 2MEO treatment, whereas the latter agent did reduce the increment in lung dry mass. The enlargement of alveolar airspaces and the decline in lung compliance were exacerbated by MP treatment. These data suggest that bleomycin-induced pulmonary fibrosis is resistant to inhibition by concurrent treatment with either glucocorticoids or 2MEO.
博来霉素诱导的小鼠肺纤维化再现了人类肺纤维化的一些关键特征，包括肺泡炎症、肌成纤维细胞增殖和胶原沉积。糖皮质激素已被用作治疗肺纤维化的一线疗法，尽管其临床疗效尚不明确。我们研究了糖皮质激素甲泼尼龙（MP）和雌激素代谢物2-甲氧基雌二醇（2MEO）对博来霉素诱导的支气管肺泡炎症、纤维化及肺功能变化的影响。博来霉素诱导纤维化的时间进程特征表明，肺干质量和羟脯氨酸含量的变化比纤维化的组织病理学评估更小。博来霉素诱导的支气管肺泡灌洗（BAL）液细胞数量和蛋白质水平的增加，不受MP（1 mg·(kg体重)(-1)·天(-1)，腹腔注射）或2MEO（50 mg·(kg体重)(-1)·天(-1)，腹腔注射）治疗的显著影响。通过组织病理学或羟脯氨酸含量测量的肺纤维化，不受MP或2MEO治疗的显著影响，而后者确实减少了肺干质量的增加。MP治疗加剧了肺泡腔扩大和肺顺应性下降。这些数据表明，博来霉素诱导的肺纤维化对糖皮质激素或2MEO联合治疗的抑制具有抗性。
