Effect of prenatal steroidal inhibition of sPLA2 in a rat model of preterm lung

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• 作者：Ana Remesal^a ; ¹ ; Daniele De Luca^b ; ^c ; ¹ ; ^{daniele.deluca@aphp.fr" class="auth_mail" title="E-mail the corresponding author} ; Laura San Feliciano^a ; Maria Isidoro-Garcia^d ; Angelo Minucci^c ; Krizia Pocino^c ; Josefina Casas^e ; Gemma Fabrias^e ; Ettore D. Capoluongo^c ; Dolores Ludena de la Cruz^a
• 关键词：Preterm neonate ; Rat ; Secretory phospholipase A2 ; Steroids ; Surfactant
• 刊名：Pulmonary Pharmacology & Therapeutics
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：36
• 期：Complete
• 页码：31-36
• 全文大小：986 K

文摘

Secretory phospholipase A2 regulates surfactant catabolism and inflammatory cascade. This enzyme is correlated with compliance, oxygenation and major outcomes in various forms of acute respiratory failure. Steroids inhibit secretory phospholipase A2 in cell culture and are widely used to boost surfactant production before preterm delivery. No data are available about the effect of antenatal steroids on secretory phospholipase A2 in the offspring: we aimed to study this effect in a rat model of preterm lung.

Material and methods

Fifteen pregnant Wistar rats were randomized to receive betamethasone, dexamethasone or placebo at 20 and 21 days gestation. Newborn rats were supported for 8 h and then sacrificed: lung tissue was analysed for secretory phospholipase A2 expression and activity, inflammatory mediators and protein content. Lipidomics was analysed using liquid chromatography-mass spectrometry.

Results

Secretory phospholipase A2 expression was significantly reduced by antenatal steroids (p < 0.001). Secretory phospholipase A2 activity, TNFα and lysophosphatidylethanolamine, a product of phospholipase reaction, were lowest in betamethasone-treated rats (p < 0.001). There was a strong correlation between secretory phospholipase A2 activity and lysophosphatidylethanolamine (r = 0.75; p = 0.001) and this remained significant after adjustment for total proteins or phospholipids.

Conclusions

Antenatal steroids decrease secretory phospholipase A2 in rat model of preterm lung.