期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 16, 期 12, 页码 3074-3084出版社
WILEY
DOI: 10.1111/j.1582-4934.2012.01588.x
关键词
high altitude pulmonary oedema; keratinocyte growth factor-2; alveolar-capillary barrier; alveolar fluid clearance; apoptosis
资金
- Shanghai Leading Academic Discipline Project [B115]
- The programme for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning
- Research Fund for the Doctoral Programme of Higher Education of China [2010072110052, 20110071120060]
- National Natural Key Science Foundation of China [30930090]
- National Natural Science Foundation of China [30871131]
High altitude pulmonary oedema (HAPE) severely affects non-acclimatized individuals and is characterized by alveolar flooding with protein- rich oedema as a consequence of blood-gas barrier disruption. Limited choice for prophylactic treatment warrants effective therapy against HAPE. Keratinocyte growth factor-2 (KGF-2) has shown efficiency in preventing alveolar epithelial cell DNA damages in vitro. In the current study, the effects of KGF-2 intratracheal instillation on mortality, lung liquid balance and lung histology were evaluated in our previously developed rat model of HAPE. We found that pre-treatment with KGF-2 (5 mg/kg) significantly decreased mortality, improved oxygenation and reduced lung wet-to-dry weight ratio by preventing alveolar-capillary barrier disruption demonstrated by histological examination and increasing alveolar fluid clearance up to 150%. In addition, KGF-2 significantly inhibited decrease of transendothelial permeability after exposure to hypoxia, accompanied by a 10-fold increase of Akt activity and inhibited apoptosis in human pulmonary microvascular endothelial cells, demonstrating attenuated endothelial apoptosis might contribute to reduction of endothelial permeability. These results showed the efficacy of KGF-2 on inhibition of endothelial cell apoptosis, preservation of alveolar-capillary barrier integrity and promotion of pulmonary oedema absorption in HAPE. Thus, KGF-2 may represent a potential drug candidate for the prevention of HAPE.
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