Effects And The Potential Mechanism Of Prenatal Sildenafil Treatment On Development Of Fetal Lung In Congenital Diaphagmatic Hernia Rat Model

The aim of the study is to investigate the effect of prenatal administration of sildenafil on the expression of hypoxia-inducible factor-2?(HIF-2?)and vascular endothelial growth factor-A(VEGF-A)in fetal lung of nitrofen induced congenital diaphragmatic hernia rat models.Ten pregnant S-D rats were randomly divided into 4 groups at 9.5 gestation day: Normal+Control group(group NC,n=2);Normal+Sildenafil group(group NS,n=2);Model+Control group(group MC,n=3);Model+Sildenafil group(group MS,n=3).Group MC and MS received 125 mg of nitrofen(dissolved in 2ml olive oil)by gastric gavage to induce CDH,group NC and NS received an equal volume of olive oil.From 11.5 d to 20.5 d of gestation,the rats in group NS and MS were administered with 30mg/kg of sildenafil every day,control group NC and MC received the same amount of distilled water.All fetuses were delivered by caesarian section at 21 d,observed the formation of diaphragmatic hernia under a magnifying glass,HE staining and histological observation of fetal lungs were performed to evaluate the maturity of lung tissue development.The general expression trend of HIF-2? and VEGF-A were detected by immunohistochemiscal staining and quantitative analysis by Western blot.There are no significant difference of CDH incidence between MC(60.53%,23/28)and MS group(72.41%,21/29)(P<0.05).The lung weight-to-body weight ratio of MC group was reduced compared with NC group(P<0.01)but no difference compared with MS group(P=0.76).Histological detection showed that the development of alveoli and vessels in fetal rats of group MC were less mature than group NC,the fetal lung maturity of MS group is between group NC and MC.Immunohistochemical staining showed that HIF-2? was highly expressed in group NC,NS and MS,the average optical...