Antenatal dexamethasone enhances surfactant protein synthesis in the hypoplastic lung of nitrofen-induced diaphragmatic hernia in rats

Abstract

Background/Purpose: Pulmonary hypoplasia is one of the main causes for the high mortality rate in patients with congenital diaphragmatic hernia (CDH). The expression of surfactant protein A in the hypoplastic CDH lung is reduced, and its concentration is decreased in the amniotic fluid of pregnancies complicated by CDH. In a CDH experimental model, prenatal glucocorticoid treatment has proved its efficacy in correcting the parameters of pulmonary biochemical and morphologic immaturity. The aim of this study was to investigate whether maternal administration of dexamethasone has any effect on the expression of surfactant protein A and surfactant protein B in nitrofen-induced experimental CDH rat model. Methods: CDH was induced in pregnant rats after administration of 100 mg of nitrofen on day 9.5 of gestation (term, 22 days). Dexamethasone (Dex, 0.25 mg/kg) was given by intraperitoneal injection on days 18.5 and 19.5 of gestation. Cesarean section was performed on day 21 of gestation. The fetuses were divided into 3 groups: group I, control (n = 16); group II, nitrofen-induced CDH (n = 16); group III, nitrofen-induced CDH with antenatal Dex treatment (n = 16). Indirect immunohistochemistry was performed using alkaline-phosphatase-coagulated streptavidin using anti-SP-A and anti-SP-B polyclonal antibodies. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate relative amount of SP-A and SP-B mRNA expression. Results: In the CDH lung (group II) we observed a markedly reduced number of type II pneumocytes positive for SP-A, and SP-B was increased to a level close to that of the control group. The relative amount of SP-A and SP-B was reduced significantly in group II compared with controls (P <.05) and significantly increased in group III compared with group II animals (P <.01). Conclusion: These results suggest that antenatal glucocorticoid treatment increases the production of surfactant proteins in the CDH hypoplastic lung. J Pediatr Surg 35:1468-1473. Copyright © 2000 by W.B. Saunders Company.