Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
Eur J Pharmacol. 2011 Dec 15;672(1-3):153-8. doi: 10.1016/j.ejphar.2011.09.183. Epub 2011 Oct 6.
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.
急性肺损伤是一种危重病综合征，其特征为急性呼吸衰竭伴双侧肺浸润，对现有治疗方法具有抗药性。急性肺损伤的特征是肺泡毛细血管屏障损伤、中性粒细胞聚集以及促炎细胞因子的诱导，随后发生破坏性肺纤维化。胃产生的酰化肽生长激素释放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。我们通过使用博来霉素诱导的小鼠急性肺损伤模型，研究了生长激素释放肽在急性肺损伤治疗中的药理学潜力。在博来霉素给药后 1 天开始，每天给小鼠给予生长激素释放肽或生理盐水。与生理盐水处理的小鼠相比，生长激素释放肽处理的小鼠具有明显更高的存活率。它们的体重和食物摄入量减少也较小。生长激素释放肽处理的小鼠的中性粒细胞肺泡浸润、肺血管通透性、促炎细胞因子的诱导以及随后的肺纤维化均有明显改善。此外，生长激素释放肽给药可减少损伤诱导的肺泡上皮细胞凋亡。我们的结果表明，生长激素释放肽通过保护肺泡上皮细胞和调节肺炎症对急性肺损伤发挥保护作用，并强调生长激素释放肽作为治疗这种难治性疾病的有前途的治疗剂。
