[Effect of ambroxol on lung development of rat models with nitrofen-induced congenital diaphragmatic hernia]

To investigate the effects of ambroxol on rat models with nitrofen-induced congenital diaphragmatic hernia (CDH) and its potential mechanism.

Nine pregnant female SD rats were randomly divided into 3 groups at Day 9.5: 2 ml olive oil intragastrically in control group (2 rats) and 200 mg nitrofen in nitrofen (2 rats) and ambroxol groups (5 rats). Antenatal ambroxol was given intraperitoneally to ambroxol group at Days 18.5, 19.5 and 20.5 of gestation while control and nitrofen groups only received intraperitoneal normal saline. At Day 21.5 the fetuses were delivered by cesarean section. Incidence of hernia, lung weight/body weight (LW/BW), mean terminal branch density (MTBD), percentage of lung alveolar area (PLAA), percentage of wall thickness (MT%) and the expression of TGF-β1 were observed.

There were 19 CDH fetuses in nitrofen group (68.4%). The incidence of hernia in ambroxol group was 65.1% (28/43). There was no significant difference (P>0.05) between two groups. LW/BW and PLAA decreased while MTBD and MT% increased significantly in the nitrofen group versus the control group [(45±6) mg/g vs (60±7) mg/g, (50.1±4.0)% vs (58.4±3.0)%, (14.0±1.8) vs (8.5±1.1), (45±6)% vs (29±6)%, all P=0.001]. After ambroxol intervention, the ambroxol group showed a higher PLAA but a lower MTBD and MT% [(54.0±2.0)%, (12.2±2.1), (39±4)%] than those in the nitrofen group (P=0.001, 0.006, 0.002). The expression of TGF-β1 in pulmonary tissues of the nitrofen group was significantly higher than that in the control group (13,594±3113 vs 9447±1355, P=0.001). It decreased after ambroxol intervention (10 015±818, P=0.01).

Though with no effect upon the occurrence of CDH in rats, the administration of ambroxol may improve the pulmonary maturity. The down-regulated expression of TGF-β1 and the oxidative stability are possible mechanisms.