The Pulmonary Changes,Expression And Significance Of CD105 In Mouse With Experimental Bronchopumonary Dysplasia

ObjectivesExposure to oxygen (FiO₂:60%) to establish the mouse model of bronchopulmonary dysplasia. To study the effect of oxygen on the pulmonary lesions,to measure the expression level of endoglin(CD105)in mouse blood and lung with bronchopulmonary dysplasia and to elucidate the relationship between the circulating level of them to discover the probable mechanism.Methods50 kunming mouse 4-days-old were divided into normoxia group (FiO₂:0.21, n=25) and oxygen group (FiO₂:60%, n=25) randomly. Mouse model of Bronchopulmonary Dysplasia is formed . The amount of CD105 was detected by using the method of enzyme linked immunosorbent assay (ELISA) on the 0 day, 7 days ,14 days ,21 days and 28 days after experiment. Morphological changes of lung tissue, measuring the thickness of respiratory membrane,radical alveolar counts were detected by stained with hematoxylin and eosin (HE), 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 expression of CD105 were detected by immunohistochemical method in different period and Statistical analysis of the correlation between them.Results1.The general state of animals rates in Oxygen groups have different degrees of poor mental response , slowly increase body weight, slowly react to stimulation, less physical activity and with varying degrees of breathlessness and cyanosis. 2.Stained by HE, lungs of oxygen group along with exposure oxygen showed destroy of alveoli, the alveolar cavity became larger, alveoli fusion and increased respiratory membrane thickness(P<0.01), alveolitis and alveolar septal fibrosis(P<0.01), along with increased numbers of local pulmonary interstitial fibroblasts. Increased pulmonary interstitial cells, radical alveolar counts were significantly lower than those in normoxia group(P<0.01) after exposure to oxygen. The pathologic changes in their lung were similar with in human when the mouse were exposed high concentration oxygen.3.CD105 concentration in the normoxia group were no significance at different time points ,whose mean values were from 264.69 ng /L to 268.55 ng /L (P > 0.05). At Oxygen exposure 7 days , CD105 concentration in oxygen group were higher significantly than that in normoxia group (346.42±14.68, P <0.01) and that were gradually rising from Oxygen group(14d: 400.25±20.10,21d: 505.15±6.15,28d: 451.88±9.96, P <0.01).4.Immunochemical stain analysis of lung tissue showed that the expression of CD105 was no significant in two groups (P >0.05) which no oxygen exposure, after Oxygen exposure 7 days(2.24±0.15, P<0.01),14 days(3.42±0.20, P<0.01), 21 days(4.35±0.18, P<0.01), 28 days(4.04±0.12, P<0.01), CD105 levels were higher significantly (P <0.001 ) than the normoxia group. CD105 weakly staining mainly located at bronchial epithelial cell,vascular endothelial cell and inierstitial of lungs at 4-28 days in some normoxia group the lung tissue.However,alveolar epithelial cells were also stained in hyperoxia group after 7 days. Compared with normoxia group,the expression of CD105-staining of lung tissues increased in hyperoxia group at postuatal 7,14,21,28 days.There were no difference between two groups on expression of CD105 at 4 days, The expression of CD105 were higher significantly in hyperoxia mice than those of normoxia mice at postnatal 7,14,21, 28 days.5.The concentration of CD105 in the serum was positive correlation with it in lung tissue in bronchopulmonary dysplasia(r =0.973).Conclusions1.The histopathological changes alveolar developmental disorders developmental delay and pulmonary microvascular fibrosis of lung injury induced by moderate concentration Oxygen (FiO₂:60%).2.The expression of CD105 in the serum was positive correlation with in lung and were gradually rising from Oxygen group.3.BPD is associated with a shift from traditional angiogenic growth factors (vascular endothelial growth factor, angiopoietin-1) to alternative regulators such as CD105, which may contribute to BPD-associated microvascular dysangiogenesis.