Expression And Effect Of HoxB5 In Neonatal Rats With Hyperoxia-induced Chronic Lung Injury

Objective: To establish the model of hyperoxia lung injury in neonatal Sprague-Dawley rats; we explored the expression of HoxB5 in chronic hyperoxia lung injury. And to investigate the dynamic changes of expression about HOXB5 ,to presume its effects on lung morphological development in neonatal rats with chronic lung injury induced by hyperoxia.Methods: 60 neonatal SD rats were separated into 2 group medially and randomly:Ⅰcontrol group (air group);Ⅱexperimental group(hyperoxia group).Every group was divided into 6 subset,each subset has 5 rats. Every rat was killed at different days, including the first 24h, 3rd, 5th, 7th, 14th day and the 21th day afte they birth. The control group was put into clear mouse cage exposed to air; the experimental group was exposed continuously to 85%～90% oxygen .The right lung was removed to made homogenate ,then measured the level of total protein(TP) content and the expression level of HOXB5 with western blot. The left lung was used for histologic examination. The immunohistochemical expression of HOXB5 was scored semiquantitatively by evaluating the intensity.Result:1.Pathologic changes in lung: at 3rd day, we could find obvious bleeding and inflammatory cells in alveolar space in hyproxia group; and at 5th day, the damage was more serious; and at 7th day, the inflammatory reaction relieved but the alveolar enlarged,the compartment became unsymmetrical,disdifferentiational alveolar was seen; at 14th day, the disordering of framework and blood vessel was mainly abnormal of lung; and at 21th day, more and more fibrous degeneration emerged within mesenchyma, elastin increased, effective alveolar for air exchange decreased, alveolar septum and small blood vessel diminished.2.TP: There were no differences in TP content at 24h after born between experimental and control group(p>0.05),at 3rd day, the TP content was higher in hyperoxia group than control group(p<0.05); at 5th day, there were no differences in TP content between two groups(p>0.05),and there were no differences in TP content between 3rd and 5th day within experimental group(p>0.05);at 7th day,it was more higher in hyperoxia group(p<0.01);and the TP content persistently increased along with more exposure time,at 21th day, the TP content was extremely higher than control group(p<0.01).3.Expression of HOXB5 protein in mice lung tissue: The expression of HOXB5 in normal neonatal rat lung in immunohistochemical and western blot show the same yo-yo transmutation, it had the most high level within the first 24h after birth; The 3rd,7th,14th,21th day after birth all had a low level except for the 5th day .And the 3rd,14th,21th day had the same expression level(p>0.05). In hyperoxia group the expression of HOXB5 show an identical change tendency but time lag. Compared to control group at 3rd ,5th,7th,14th day the hyperoxia group had a significant quantity change: more, less, more and more (p<0.05), however the end of the first 24h and the 21th day after birth had the same level(p>0.05). there was no discrepancy between the 5th day in hyperoxia group and the 3rd day in control group, so was the 7th day in hyperoxia group and the 5th day in control group (p>0.05).Conclusions: The neonatal rat of chronic lung injury induced by hyperoxia characterized by inflammatory reaction, decreased and simple formation alveolus, disordered pneumoangiogram and so on .The TP content in lung homogenate increased along with the hyperoxia exposure. The raise at the 3rd day after birth illustrated that acute inflammatory reaction took place in nonage of hyperoxia exposure. The raise at the 7th day prompted that the ingredient of lung has changed within the process of chronic lung injury induced by hyperoxia. The expression of HOXB5 protein display a yo-yo transmutation discover it paly a different role in the differentiation and development of lung at different time. And the expression of HOXB5 protein show the same dynamic change in control group but time lag illustrated that HOXB5 took a very important role in the process of hyperoxia-induced chronic lung injury in neonatal rats. The disordered form of branching and alveolus confirmed the considerable contribution of HOXB5 protein. All conclusions we got provid a rationale of mechanism of clinical hyperoxia-induced chronic lung injury in neonatal intensive care unit (NICU).