博莱霉素
肺纤维化
纤维化
医学
兴奋剂
肺
受体
体内
特发性肺纤维化
内科学
药理学
生物
化疗
生物技术
作者
Ádám Hosszú,Dóra Balogh,Akos Roland Toth,Kata Csekő,Judit Hodrea,Zsuzsanna Helyes,Attila J. Szabó,Andrea Fekete
标识
DOI:10.1183/13993003.congress-2023.pa2364
摘要
Introduction and aims: Idiopathic pulmonary fibrosis is associated with a median survival of just 2-3 years after diagnosis. Current therapies ameliorate pulmonary functional decrement, but do not inhibit the progression of fibrosis or reduce mortality. Thus, effective anti-fibrotic therapies are desperately needed. Based on our previous results in other organs, we aimed to investigate whether Sigma-1 receptor (S1R) agonist fluvoxamine (FLU) can ameliorate pulmonary fibrosis. Methods: Pulmonary fibrosis was induced in wt and S1R-/- mice by oropharyngeal bleomycin (BLM) administration. Mice were treated daily with FLU and sacrificed after 21 days. Pulmonary functional parameters were measured by whole-body plethysmography. Results: After 21 days pro-fibrotic factor Tgfb expression was unaltered, while Ctgf expression increased in the BLM group, but not in the wt BLM+FLU group. Elevated expressions of ECM components collagen I, collagen III and fibronectin were reduced to control levels in wt BLM+FLU mice. Evaluation of Masson9s trichrome-stained sections underlined the massive anti-fibrotic effect of FLU. In vivo MicroCT showed more preserved aerated tissue area in wt BLM+FLU vs. wt BLM and S1R-/- BLM+FLU. Breathing rate increased in all groups at day 7 and normalized only in wt BLM+FLU mice by day 21. On day 7 tidal volume and minute volume were preserved in wt FLU-treated mice only, while decreased in wt BLM and S1R-/- BLM+FLU. Peak inspiratory flow and peak expiratory flow were more preserved in wt BLM+FLU mice on day 7 and returned to baseline by day 21 in all groups. Conclusions: Based on our preclinical data S1R may be a novel, effective drug target in the treatment of pulmonary fibrosis.
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