Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Republic of Korea.
Exp Mol Med. 2018 Nov 14;50(11):1-10. doi: 10.1038/s12276-018-0178-y.
Although the positive effects of recombinant fibroblast growth factor-2 (rFGF-2) in chronic obstructive pulmonary disease (COPD) have been implicated in previous studies, knowledge of its role in COPD remains limited. The mechanism of FGF2 in a COPD mouse model and the therapeutic potential of rFGF-2 were investigated in COPD. The mechanism and protective effects of rFGF-2 were evaluated in cigarette smoke-exposed or elastase-induced COPD animal models. Inflammation was assessed in alveolar cells and lung tissues from mice. FGF-2 was decreased in the lungs of cigarette smoke-exposed mice. Intranasal use of rFGF-2 significantly reduced macrophage-dominant inflammation and alveolar destruction in the lungs. In the elastase-induced emphysema model, rFGF-2 improved regeneration of the lungs. In humans, plasma FGF-2 was decreased significantly in COPD compared with normal subjects (10 subjects, P = 0.037). The safety and efficacy of inhaled rFGF-2 use was examined in COPD patients, along with changes in respiratory symptoms and pulmonary function. A 2-week treatment with inhaled rFGF-2 in COPD (n = 6) resulted in significantly improved respiratory symptoms compared with baseline levels (P < 0.05); however, the results were not significant compared with the placebo. The pulmonary function test results of COPD improved numerically compared with those in the placebo, but the difference was not statistically significant. No serious adverse events occurred during treatment with inhaled rFGF-2. The loss of FGF-2 production is an important mechanism in the development of COPD. Inhaling rFGF-2 may be a new therapeutic option for patients with COPD because rFGF-2 decreases inflammation in lungs exposed to cigarette smoke.
尽管先前的研究表明重组成纤维细胞生长因子-2（rFGF-2）对慢性阻塞性肺疾病（COPD）有积极影响，但人们对其在 COPD 中的作用仍知之甚少。本研究旨在探讨 FGF2 在 COPD 小鼠模型中的作用及其治疗潜力。在 COPD 中，评估了 rFGF-2 在香烟烟雾暴露或弹性蛋白酶诱导的 COPD 动物模型中的作用机制和保护作用。在肺泡细胞和肺组织中评估了炎症。在香烟烟雾暴露的小鼠肺部，FGF-2 减少。鼻腔内使用 rFGF-2 可显著减少肺部巨噬细胞主导的炎症和肺泡破坏。在弹性蛋白酶诱导的肺气肿模型中，rFGF-2 改善了肺部的再生。在人类中，与正常受试者相比，COPD 患者的血浆 FGF-2 明显降低（10 例，P=0.037）。评估了吸入 rFGF-2 在 COPD 患者中的安全性和疗效，以及呼吸症状和肺功能的变化。在 COPD 患者中进行为期 2 周的吸入 rFGF-2 治疗，与基线水平相比，呼吸症状显著改善（P<0.05）；然而，与安慰剂相比，结果无统计学意义。与安慰剂相比，COPD 的肺功能测试结果数值上有所改善，但差异无统计学意义。在吸入 rFGF-2 治疗期间未发生严重不良事件。FGF-2 产生的丧失是 COPD 发展的一个重要机制。吸入 rFGF-2 可能是 COPD 患者的一种新的治疗选择，因为 rFGF-2 可减轻暴露于香烟烟雾的肺部炎症。
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