PDF(Pubmed)
Abstract：
Glucagon-like peptide-1 (GLP-1) has proven to be protective in animal models of lung disease but the underlying mechanisms are unclear. Atrial natriuretic peptide (ANP) is mainly produced in the heart. As ANP possesses potent vaso- and bronchodilatory effects in pulmonary disease, we hypothesised that the protective functions of GLP-1 could involve potentiation of local ANP secretion from the lung. We examined whether the GLP-1 receptor agonist liraglutide was able to improve oxygenation in lungs exposed to 2 h of warm ischemia and if liraglutide stimulated ANP secretion from the lungs in the porcine ex vivo lung perfusion (EVLP) model. Pigs were given a bolus of 40 µg/kg liraglutide or saline 1 h prior to sacrifice. The lungs were then left in vivo for 2 h, removed en bloc and placed in the EVLP machinery. Lungs from the liraglutide treated group were further exposed to liraglutide in the perfusion buffer (1.125 mg). Main endpoints were oxygenation capacity, and plasma and perfusate concentrations of proANP and inflammatory markers. Lung oxygenation capacity, plasma concentrations of proANP or concentrations of inflammatory markers were not different between groups. ProANP secretion from the isolated perfused lungs were markedly higher in the liraglutide treated group (area under curve for the first 30 min in the liraglutide group: 635 ± 237 vs. 38 ± 38 pmol/L x min in the saline group) (p < 0.05). From these results, we concluded that liraglutide potentiated local ANP secretion from the lungs.
摘要：
胰高血糖素样肽-1（GLP-1）已被证明在肺部疾病的动物模型中具有保护性，但其潜在机制尚不清楚。心房利钠肽(ANP)主要产生于心脏。由于ANP在肺部疾病中具有有效的血管和支气管扩张作用，我们假设GLP-1的保护功能可能涉及肺局部ANP分泌的增强.我们在猪离体肺灌注（EVLP）模型中检查了GLP-1受体激动剂利拉鲁肽是否能够改善暴露于2小时热缺血的肺中的氧合，以及利拉鲁肽是否刺激肺的ANP分泌。在处死前1小时给予猪40µg/kg利拉鲁肽或盐水的推注。然后将肺留在体内2小时，整体移除并放置在EVLP机械中。利拉鲁肽处理组的肺进一步暴露于灌注缓冲液(1.125mg)中的利拉鲁肽。主要终点是氧合能力，血浆和灌注液浓度的proANP和炎症标志物。肺氧合能力，proANP的血浆浓度或炎症标志物的浓度在组间没有差异.利拉鲁肽治疗组分离的灌注肺的ProANP分泌明显更高（利拉鲁肽组前30分钟的曲线下面积：635±237vs.生理盐水组38±38pmol/L×min(p<0.05)。从这些结果来看,我们得出的结论是利拉鲁肽增强了肺部局部ANP分泌。
