Author:
Chen Xueyu,Han Dongshan,Wang Xuan,Huang Xuemei,Huang Zilu,Liu Yijun,Zhong Junyan,Walther Frans J.,Yang Chuanzhong,Wagenaar Gerry T. M.
Abstract
Abstract
Background
Ibuprofen is a nonsteroidal anti-inflammatory drug that is commonly used to stimulate closure of a patent ductus arteriosus (PDA) in very premature infants and may lead to aberrant neonatal lung development and bronchopulmonary dysplasia (BPD).
Methods
We investigated the effect of ibuprofen on angiogenesis in human umbilical cord vein endothelial cells (HUVECs) and the therapeutic potential of daily treatment with 50 mg/kg of ibuprofen injected subcutaneously in neonatal Wistar rat pups with severe hyperoxia-induced experimental BPD. Parameters investigated included growth, survival, lung histopathology and mRNA expression.
Results
Ibuprofen inhibited angiogenesis in HUVECs, as shown by reduced tube formation, migration and cell proliferation via inhibition of the cell cycle S-phase and promotion of apoptosis. Treatment of newborn rat pups with ibuprofen reduced pulmonary vessel density in the developing lung, but also attenuated experimental BPD by reducing lung inflammation, alveolar enlargement, alveolar septum thickness and small arteriolar wall thickening.
Conclusions
In conclusion, ibuprofen has dual effects on lung development: adverse effects on angiogenesis and beneficial effects on alveolarization and inflammation. Therefore, extrapolation of the beneficial effects of ibuprofen to premature infants with BPD should be done with extreme caution.
Funder
Guangdong Basic and Applied Basic Research Foundation
Shenzhen Science and Technology Program
Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties
Publisher
Springer Science and Business Media LLC
Cited by
3 articles.
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