OBJECTIVETo study the protective effect of the prenatal use of tetrandrine (TET) against congenital diaphragmatic hernia (CDH) in rats and possible mechanisms.

METHODSPregnant female Sprague-Dawley rats were randomly divided into 3 groups: control, nitrofen and TET treatment. The later two groups were administered with nitrofen by gavage on day 9.5 of gestation. On day 18.5 of gestation, TET (30 mg/kg) was given by gavage (once a day, for three days) in the TET treatment group. On day 21 of gestation, parts of pregnant rats were delivered by cesarean section and amniotic fluid was collected. The fetal rats were examined for a diaphragmatic hernia. Lung histologic evaluations with microscope and immunohistochemistry staining of TNF-α were performed. TNF-α in amniotic fluid was detected using ELISA. The remaining pregnant rats were allowed to deliver spontaneously at term. The survival of pup rats was observed until 24 hrs of age.

RESULTSIn the nitrofen group, significant lung hypoplasia was presented not only in fetuses with CDH but also in those without CDH. Stronger expression of TNF-α was observed in fetal lungs and amniotic fluid in the nitrofen group, even when CDH was absent. The TET treatment group showed improved lung development compared with the nitrofen group. The incidence of large diaphragmatic hernia in the TET treatment group was lower than that in the nitrofen group (P<0.05), and the expression of TNF-α in fetal lungs and amniotic fluid in the TET treatment group was also lower than in the nitrofen group (P<0.01). The 24-hr survival rate of pup rats in the TET group was higher than that in the nitrofen group (P<0.01).

CONCLUSIONSPrenatal use of TET can improve nitrofen-induced pulmonary hypoplasia, decrease the incidence of large diaphragmatic hernia and increase the survival rate of pup rats, possibly through a reduction in the production of TNF-α in fetal lungs and amniotic fluid in rats with CDH.