ABSTRACT
Objective To study the effects of cystic fibrosis transmembrane conductance regulator (CFTR) on neonatal rats with bronchopulmonary dysplasia (BPD).Method The hyperoxia (FiO2＞ 90％)-induced neonatal BPD rat models were established and assigned into three groups:the model group,the agonist group and the antagonist group.Room air (FiO2 21％) was inhaled by the rats in the control group.50 μl of phosphate buffered saline (PBS),genistein (50 mg/kg),arachidonic acid (500 mg/kg) and PBS were injected intraperitoneally respectively in the model group,the agonist group,the antagonist group and the control group at 24,48 and 72 h after birth.The survival rates of the neonatal rats were calculated,the survival curves were drawn,the pathological changes of the lung tissues were examined (the control group and the model group:3,14 and 21 d after birth;the agonist group and antagonist group:14 and 21 d after birth),and the expression of CFTR were studied using western blot method.The acute lung injury scores of the model group,the agonist group and the antagonist group were compared and the gray value was analyzed using Graphpad software.Result (1) The survival rates in the control group,the model group,the agonist group and the antagonist group were 96.8％,93.3％,100％ and 34.5％ respectively.The antagonist group had significantly lower survival rate than the other three groups (P＜0.001).(2)The alveoli developed gradually with age in the control group.The pulmonary pathology of the model group showed:alveolar congestion,hemorrhage,infiltration or aggregation of neutrophils in airspace or vessel wall,thickness of alveolar wall,with some enlarged alveolar spaces and reduced alveolar cavities.As the inflammation gradually decreased,some alveolar spaces significantly enlarged and the numbers of alveolar cavities significantly reduced.No significant differences existed of the acute lung injury scores among the agonist group,the antagonist group and the model group at 14 and 21 d after birth (P＞0.05).(3) The expressions of CFTR in the lungs were lower in the model group than the control group 3 d after birth (P＜0.01).No significant differences existed of the CFTR expression between the model group and the control group 14 d after birth(P＞0.05).The CFTR expression was much higher in the agonist group than the model group (P＜0.01) and also higher in the antagonist group than the model group (P＜0.05) 14 d after birth.The CFTR expression was lower in the model group than the control group,and higher in the agonist group than the model group 21 d after birth (P＜ 0.05).No significant differences existed of CFTR expression between the antagonist group and the model group 21 d after birth (P＞0.05).Conclusion CFTR may play a protective role in the pathogenesis of BPD.