雾化的过氧化物酶体增殖物激活受体γ激动剂：增强新生大鼠肺成熟和损伤修复的新方法。
Nebulized PPARγ agonists: a novel approach to augment neonatal lung maturation and injury repair in rats.
作者信息
Morales Edith, Sakurai Reiko, Husain Sumair, Paek Dave, Gong Ming, Ibe Basil, Li Yishi, Husain Maleha, Torday John S, Rehan Virender K
机构信息
1] Department of Pediatrics, Harbor-University of California Los Angeles (UCLA) Medical Center, Los Angeles Biomedical Research Institute, David Geffen School of Medicine at UCLA, Torrance, California [2] Department of Pediatrics, Children's Hospital Orange County, Orange, California.
Department of Pediatrics, Harbor-University of California Los Angeles (UCLA) Medical Center, Los Angeles Biomedical Research Institute, David Geffen School of Medicine at UCLA, Torrance, California.
出版信息
Pediatr Res. 2014 May;75(5):631-40. doi: 10.1038/pr.2014.8. Epub 2014 Jan 31.
BACKGROUND
By stimulating lipofibroblast maturation, parenterally administered peroxisome proliferator-activated receptor γ (PPARγ) agonists promote lung homeostasis and injury repair in the neonatal lung. In this study, we determined whether PPARγ agonists could be delivered effectively via nebulization to neonates, and whether this approach would also protect against hyperoxia-induced lung injury.
METHODS
One-day old Sprague-Dawley rat pups were administered PPARγ agonists rosiglitazone (RGZ, 3 mg/kg), pioglitazone (PGZ, 3 mg/kg), or the diluent, via nebulization every 24 h; animals were exposed to 21% or 95% O2 for up to 72 h. Twenty-four and 72 h following initial nebulization, the pups were sacrificed for lung tissue and blood collection to determine markers of lung maturation, injury repair, and RGZ and PGZ plasma levels.
RESULTS
Nebulized RGZ and PGZ enhanced lung maturation in both males and females, as evidenced by the increased expression of markers of alveolar epithelial and mesenchymal maturation. This approach also protected against hyperoxia-induced lung injury, since hyperoxia-induced changes in bronchoalveolar lavage cell and protein contents and lung injury markers were all blocked by nebulized PGZ.
CONCLUSION
Nebulized PPARγ agonist administration promotes lung maturation and prevents neonatal hyperoxia-induced lung injury in both males and females.
背景
通过刺激脂肪成纤维细胞成熟，经肠外给予过氧化物酶体增殖物激活受体γ（PPARγ）激动剂可促进新生鼠肺的稳态维持和损伤修复。在本研究中，我们确定PPARγ激动剂是否可通过雾化有效递送至新生鼠，以及这种方法是否也能预防高氧诱导的肺损伤。
方法
对1日龄的斯普拉格-道利大鼠幼崽每24小时通过雾化给予PPARγ激动剂罗格列酮（RGZ，3毫克/千克）、吡格列酮（PGZ，3毫克/千克）或稀释剂；动物暴露于21%或95%氧气中长达72小时。在首次雾化后24小时和72小时，处死幼崽以收集肺组织和血液，以测定肺成熟、损伤修复的标志物以及RGZ和PGZ的血浆水平。
结果
雾化的RGZ和PGZ均增强了雄性和雌性幼崽的肺成熟，肺泡上皮和间充质成熟标志物的表达增加证明了这一点。这种方法还能预防高氧诱导的肺损伤，因为雾化的PGZ可阻断高氧诱导的支气管肺泡灌洗细胞和蛋白质含量变化以及肺损伤标志物。
结论
雾化给予PPARγ激动剂可促进肺成熟，并预防雄性和雌性新生鼠高氧诱导的肺损伤。
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