title: Keratinocyte growth factor-2 intratracheal instillation significantly attenuates ventilator-induced lung injury in rats.
abstract: Preservation or restoration of normal alveolar epithelial barrier function is crucial for pulmonary oedema resolution. Keratinocyte growth factor-2 (KGF-2), a potent epithelial cell mitogen, may have a role in preventing ventilator-induced lung injury (VILI), which occurs frequently in mechanically ventilated patients. The aim of the study was to test the role of KGF-2 in VILI in rats. Forty healthy adult male Sprague-Dawley rats were randomly allocated into four groups, where rats in Groups HVZP (high-volume zero positive end-expiratory pressure) and HVZP+KGF-2 were given intratracheally equal PBS and 5 mg/kg KGF-2 72 hrs before 4 hrs HVZP ventilation (20 ml/kg), respectively, while PBS and KGF-2 were administered in the same manner in Groups Control and KGF-2, which underwent tracheotomy only with spontaneous breathing. Inflammatory cytokines (tumour necrosis factor-α, macrophage inflammatory protein 2), neutrophil and total protein levels in bronchoalveolar lavage fluid and surfactant protein mRNA expression in lung tissue were detected; the number of alveolar type II cells, lung water content and lung morphology were also evaluated. The results indicate that pre-treatment with KGF-2 showed dramatic improvement in lung oedema and inflammation compared with HVZP alone, together with increased surfactant protein mRNA and alveolar type II cells. Our results suggest that KGF-2 might be considered a promising prevention for human VILI or other acute lung injury diseases.
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bi
authors.forename: Lin
authors.initials: L
authors.lastname: Tong
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Zhu
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.forename: Chunxue
authors.initials: C
authors.lastname: Bai
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Song
authors.forename: Jun
authors.initials: J
authors.lastname: She
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D051526:Fibroblast Growth Factor 10 / Q000008:administration & dosage*; D006801:Humans; D007124:Immunoenzyme Techniques; D007442:Intubation, Intratracheal; D008297:Male; D046529:Microscopy, Electron, Transmission; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055397:Ventilator-Induced Lung Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D051526:Fibroblast Growth Factor 10; D012333:RNA, Messenger
keywords: alveolar type II cell; inflammatory cytokines; keratinocyte growth factor-2; mechanical ventilation; surfactant protein