Author:
You Kai,Xu Xuewen,Fu Jianhua,Xu Shuyan,Yue Xiaohong,Yu Zhiling,Xue Xindong
Abstract
Abstract
Background
Prolonged exposure to hyperoxia in neonates can cause hyperoxic acute lung injury (HALI), which is characterized by increased pulmonary permeability and diffuse infiltration of various inflammatory cells. Disruption of the epithelial barrier may lead to altered pulmonary permeability and maintenance of barrier properties requires intact epithelial tight junctions (TJs). However, in neonatal animals, relatively little is known about how the TJ proteins are expressed in the pulmonary epithelium, including whether expression of TJ proteins is regulated in response to hyperoxia exposure. This study determines whether changes in tight junctions play an important role in disruption of the pulmonary epithelial barrier during hyperoxic acute lung injury.
Methods
Newborn rats, randomly divided into two groups, were exposed to hyperoxia (95% oxygen) or normoxia for 1–7 days, and the severity of lung injury was assessed; location and expression of key tight junction protein occludin and ZO-1 were examined by immunofluorescence staining and immunobloting; messenger RNA in lung tissue was studied by RT-PCR; transmission electron microscopy study was performed for the detection of tight junction morphology.
Results
We found that different durations of hyperoxia exposure caused different degrees of lung injury in newborn rats. Treatment with hyperoxia for prolonged duration contributed to more serious lung injury, which was characterized by increased wet-to-dry ratio, extravascular lung water content, and bronchoalveolar lavage fluid (BALF):serum FD4 ratio. Transmission electron microscopy study demonstrated that hyperoxia destroyed the structure of tight junctions and prolonged hyperoxia exposure, enhancing the structure destruction. The results were compatible with pathohistologic findings. We found that hyperoxia markedly disrupted the membrane localization and downregulated the cytoplasm expression of the key tight junction proteins occludin and ZO-1 in the alveolar epithelium by immunofluorescence. The changes of messenger RNA and protein expression of occludin and ZO-1 in lung tissue detected by RT-PCR and immunoblotting were consistent with the degree of lung injury.
Conclusions
These data suggest that the disruption of the pulmonary epithelial barrier induced by hyperoxia is, at least in part, due to massive deterioration in the expression and localization of key TJ proteins.
Publisher
Springer Science and Business Media LLC
Reference45 articles.
1. Jobe AH, Bancalari E: Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001, 163: 1723-1729.
2. Bancalari E, Claure N, Sosenko IR: Bronchopulmonary dysplasia: changes in pathogenesis, epidemiology and definition. Semin Neonatol. 2003, 8: 63-71. 10.1016/S1084-2756(02)00192-6.
3. Smith VC, Zupancic JA, McCormick MC, Croen LA, Greene J, Escobar GJ, Richardson DK: Rehospitalization in the first year of life among infants with bronchopulmonary dysplasia. J Pediatr. 2004, 144: 799-803.
4. Doyle LW: Respiratory function at age 8–9 years in extremely low birthweight/very preterm children born in Victoria in 1991–1992. Pediatr Pulmonol. 2006, 41: 570-576. 10.1002/ppul.20412.
5. Doyle LW, Faber B, Callanan C, Freezer N, Ford GW, Davis NM: Bronchopulmonary dysplasia in very low birth weight subjects and lung function in late adolescence. Pediatrics. 2006, 118: 108-113. 10.1542/peds.2005-2522.
Cited by
67 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献