标题：Sildenafil ameliorated meconium-induced acute lung injury in a neonatal rat model
作者：Song, Jia; Wang, Yang-Yang; Song, Ping; Li, Lu-Peng; Fan, You-Fei; Wang, Yu-Lin
作者机构：[Song, Jia; Fan, You-Fei; Wang, Yu-Lin] Shandong Univ, Dept Pediat, Shandong Prov Hosp, 324 Jingwu Rd, Jinan 250021, Peoples R China.; [Wang, Yang-Y 更多
通讯作者地址：[Wang, YL]Shandong Univ, Dept Pediat, Shandong Prov Hosp, 324 Jingwu Rd, Jinan 250021, Peoples R China.
来源：INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE
关键词：Meconium aspiration; lung injury; sildenafil; inflammation; oxidative; stress; apoptosis
摘要：Background: Meconium aspiration syndrome (MAS) remains one of the principle causes of neonatal death. Inflammation, oxidation and apoptosis play a crucial role in the pathophysiology of MAS. This study aimed to evaluate the effect of phosphodiesterase-5 inhibitor sildenafil in meconium-induced lung injury. Methods: Twenty-four neonatal Wistar rats were randomly divided into M (meconium), S (sildenafil), D (dexamethasone) and C (control) groups. Acute lung injury was induced by endotracheal instillation of human meconium (60 mg/ml, 2 ml/kg). After meconium instillation, rats in the S and D groups received sildenafil (25 mg/kg, ig.) and dexamethasone (1 mg/kg, ig.), respectively; while rats in the C and M groups both received saline (2 ml/kg, ig.). Rats were sacrificed at six hours for histopathological, biochemical, immunohistochemical and TUNEL analyses of lung damage indicators. Results: We found that sildenafil treatment attenuated meconium-induced acute lung injury as evaluated by histopathological changes and lung injury score. Sildenafil administration reduced meconium-induced inflammation as measured by myeloperoxidase (MPO) activity in lungs and tumor necrosis factor-alpha (TNF-alpha) levels in serum, suppressed oxidative stress as assessed by nitric oxide (NO) levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in lung tissues, and attenuated apoptosis as assayed by pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) products in lung tissues. In addition, sildenafil increased cAMP and cGMP levels in serum. Conclusion: These results indicate that sildenafil could protect meconium-induced lung injury through the inhibition of inflammation, oxidative stress and apoptosis.