18:1/18:1-Dioleoyl-phosphatidylglycerol prevents alveolar epithelial apoptosis and profibrotic stimulus in a neonatal piglet model of acute respiratory distress syndrome

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• 作者：Stefanie Preuß ; ^a ; Julia Scheiermann^a ; Sabrina Stadelmann^a ; Friede D. Omam^a ; Supandi Winoto-Morbach^b ; Dennis Lex^d ; Philipp von Bismarck^a ; Sabine Adam-Klages^b ; Friederike Knerlich-Lukoschus^c ; Daniela Wesch^b ; Janka Held-Feindt^c ; Stefan Uhlig^d ; Stefan Schü ; tze^b ; Martin F. Krause^a ; ^{m.krause@pediatrics.uni-kiel.de" class="auth_mail}
• 关键词：Secretory phospholipase A2 ; (Neonatal) acute respiratory distress syndrome ; Airway epithelial cells ; Epithelial-to-mesenchymal transition ; Phosphatidylglycerols ; Fibrous lung repair
• 刊名：Pulmonary Pharmacology & Therapeutics
• 出版年：June 2014
• 年：2014
• 卷：28
• 期：1
• 页码：25-34
• 全文大小：1926 K

文摘

18:1/18:1-Dioleoyl-phosphatidylgycerol (DOPG) is a surfactant phospholipid that is nearly non-detectable in neonatal surfactant films. When alveolar macrophages are exposed to DOPG in vitro, secretory phospholipase A2 (sPLA2) production is blocked, resulting in suppressed macrophage activity and improved surfactant function. We investigated whether the addition of DOPG to a commercially available surfactant preparation would improve lung function in a neonatal piglet model of acute respiratory distress syndrome.

Materials and methods

Respiratory failure was achieved by triple-hit lung injury (repeated broncho-alveolar lavage, injurious ventilation, tracheal lipopolysaccharide instillation, each intervention 24 h apart) in twenty-four domestic piglets aged 2–6 days and subject to mechanical ventilation. Following each lung injury protocol the piglets were treated with surfactant alone or with surfactant + DOPG.

Results

Within 72 h of mechanical ventilation, we observed significantly improved gas exchange (oxygenation and ventilation), lung mechanics (compliance and resistance of the respiratory system), and pulmonary oedema (extra-vascular lung water index) in the surfactant + DOPG group. This favourable clinical effect could be attributed to improved surfactant function, reduced sPLA2 secretion, inhibition of macrophage migration, reduced alveolar epithelial apoptosis, and suppression of amphiregulin and TGF-尾1 expression in pulmonary tissues as a prerequisite for fibrous lung repair.

Conclusions

We conclude that surfactant fortified by DOPG preserves lung function, and prevents alveolar epithelial injury and fibrous stimulus by reduction of sPLA2 in a neonatal model of acute respiratory distress syndrome without any relevant discernable side effects. Hence, DOPG supplementation in a neonatal lung exerts important function protecting effects and seems to be justified in cases of overwhelming pulmonary inflammation.