Effect Of Prolonged Hyperoxia Exposure On Glucocorticoid In Serum And Glucocorticoid Receptor In The Lung With Preterm Rats

ObjetiveWe investigated the effects of prolonged hyperoxia exposure on glucocorticoid in serum (GC)and glucocorticoid receptor (GR) in the lung with preterm rats, and discussed the relationship between bronchopulmonary dysplasia ( BPD) and the changes of GC in serum and GC in the lung.MeithodsThe preterm rats at 21 - d gestation were assigned randomly into hyperoxia group and control group. The preterm rat pups in hyperoxia group inhaled high concentration oxygen ( > 90% ) continuously, and the preterm rat pups in control group inhaled atmosphere. Randomly selected animals from each group at postnatal 1,3,7', 14 and 21 day were killed with an overdose of chloral hydrate (10% , 1 ml/kg). Similarly oriented lung section from the left lung was prepared for hematoxylin-eosin ( HE) staining. Each microscopic field was evaluated for the absence (score 0) or presence of alveolar septal fibrosis(score 1 for mild, score 2 for moderate, and score 3 for marked) according to the review article by Stocker. The concentrations of GC in serum were measured by radioim-munoanalysis at postnatal 3,7, and 14 days. The expressions of GR in the lung were measured by immunochemical method and western blot analysis at postnatal 1,3,7, 14 and 21 days, and the values of glucocorticoid receptor were assessed with semi-quantitative analysis by photographic analysis system.ResultsAlveolar epithelial cells and endothelium in the capillary were damaged,and inflammation cells, neutrophil, etc. infiltrated into pulmonary alveolar septum or alveolar space at early stage in experimental preterm rats. At last stage, the thickness of alveolar septum increased following fibrosis. These changes were in accord with the pathologic changes of BPD. The serum cortisol concentrations in control group were no significance at different time points, whose mean values were from 16.5ng/ml to 18.0ng/ml. At postnatal 3 days, the serum cortisol concentration was similar between both groups ( n = 25, P = 0.56 ). The serum cortisol concentration in experimental group was higher significantly than that in control group at postnatal 7d (n=25, P=0.04), and was lower significantly than that in control group at postnatal 14d (n =21, P =0.0018). Irnmunochemical stain analysis of lung tissue showed that the expression of GRs in the lung of control preterm rats increased gradually within postnatal 1 week, and then decreased to the stable level gradually after postnatal 1 week. The expression of GRs in the lung of experimental group were no difference at postnan-tal 1 and 3 days in comparison with the control groups (n=8,P>0. 05). At postnatal 7d, the expression of GRs in the lung of experimental group was significant lower than those in the lung of control group ( n = 8, p = 0.003 ). At postnatal 14 and 21 days, there was no sijgnificant difference between two groups due to the low expression of GR in control group (n=8, P > 0. 05 ). The results from western blot analysis were similar with those from immunochemical analysis at the same time points.ConclusionThe pathologic changes in their lung were similar with BPD in human when the preterm rats are exposed high concentration oxygen. Serum cortisol and GR of lung changed significantly after the rats inhaled high concentration oxygen. Abnormal GG secretion and GR expression may play an important role in BPD. Therefore, we don't misuse GC to therapy BPD.