Ghrelin ameliorates bleomycin-induced acute lung injury by protecting alveolar epithelial cells and suppressing lung inflammation
Ghrelin ameliorates bleomycin-induced acute lung injury by protecting alveolar epithelial cells and suppressing lung inflammation
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DOI：
10.1016/j.ejphar.2011.09.183
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发表时间：
2011-12-15
影响因子：
5
通讯作者：
Nakazato, Masamitsu
中科院分区：
文献类型：
--
作者：
Imazu, Yoshifumi;Yanagi, Shigehisa;Nakazato, Masamitsu
急性肺损伤是一种危重病综合征，由急性呼吸衰竭伴双侧肺浸润组成，目前的治疗方法难以治愈。急性肺损伤的特征在于肺泡毛细血管屏障的损伤、中性粒细胞积聚和促炎细胞因子的诱导，随后是破坏性的肺纤维化。胃饥饿素是一种在胃中产生的酰化肽，可增加食物摄入和生长激素分泌，抑制炎症，促进细胞存活。我们使用博莱霉素诱导的小鼠急性肺损伤模型研究了Ghrelin在治疗急性肺损伤中的药理学潜力。在博来霉素施用后1天开始每天向小鼠给予Ghrelin或盐水。Ghrelin治疗的小鼠显示出比盐水治疗的小鼠更高的存活率。他们的体重和食物摄入量也有较小的减少。在Ghrelin治疗的小鼠中，中性粒细胞肺泡浸润、肺血管通透性、促炎细胞因子的诱导和随后的肺纤维化的改善是显著的。此外，ghrelin管理减少损伤诱导的肺泡上皮细胞凋亡。我们的研究结果表明，生长激素释放肽管理发挥保护作用，对急性肺损伤，保护肺泡上皮细胞和调节肺部炎症，并强调生长激素释放肽作为一个有前途的治疗药物，用于管理这种难治性疾病。(C)2011 Elsevier B.V.保留所有权利。
Acute lung injury is a critical illness syndrome consisting of acute respiratory failure with bilateral pulmonary infiltrates that is refractory to current therapies. Acute lung injury is characterized by injury of the alveolar capillary barrier, neutrophil accumulation, and induction of pro-inflammatory cytokines followed by devastating lung fibrosis. Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation, and promotes cell survival. We investigated the pharmacological potential of ghrelin in the treatment of acute lung injury by using a bleomycin-induced acute lung injury model in mice. Ghrelin or saline was given to mice daily starting 1 day after bleomycin administration. Ghrelin-treated mice showed a definitively higher survival rate than saline-treated ones. They also had smaller reductions in body weight and food intake. The amelioration of neutrophil alveolar infiltration, pulmonary vascular permeability, induction of pro-inflammatory cytokines, and subsequent lung fibrosis were notable in ghrelin-treated mice. Additionally, ghrelin administration reduced the injury-induced apoptosis of alveolar epithelial cells. Our results indicate that ghrelin administration exerts a protective effect against acute lung injury by protecting the alveolar epithelial cells and regulating lung inflammation, and highlight ghrelin as a promising therapeutic agent for the management of this intractable disease. (C) 2011 Elsevier B.V. All rights reserved.