The effect of prenatal Tetrandrine treatment on pulmonary hypoplasia in fetal rats with nitrofen-induced congenital diaphragmatic hernia

Abstract

Objective To investigate the effects of prenatal tetrandrine (TET) treatment on the expression of surfactant protein B (SP-B) and proliferation cell nuclear antigen (PCNA) in lung tis-sues of fetal rats with nitrofen-induced congenital diaphragmatic hernia (CDH). Methods Ten preg-nant female Sprague-Dawley rats were randomly divided into 3 groups: Control group (n = 2),CDH group (n = 4) and TET group (n = 4). The rats of CDH group and TET group were administered with 125 mg nitrofen dissolved in 3.0 ml olive oil by gastric gavage. The same volume of olive oil was given to the rats of Control group. From gestation day 18.5,30 mg TET was administered by gastric gavage to the TET group rats once a day for three days. Same dose of natural saline was given to the rats of Control group and CDH group. On day 21 of gestation,all the fetuses were delivered by cesarean sec-tion. The rat fetuses were sacrificed and examined for diaphragmatic hernia. Lung histological studies were made on H&E staining slides. Immunohistochemical staining was performed to detect SP-B and PCNA in lung tissues. Results Of the 74 fetuses harvested from the rats of CDH and TET groups,CDH was found on 48 fetuses of (64.9%). The incidence of CDH between CDH group and TET group was similar (P>0.05). Hypoplastic lungs were noted on the fetal rats of CDH group. Im-proved lung development was found on TET group fetal rats. On the rats of control group,strong ex-pression of SP-B was found in the alveolar and distal bronchial epithelium,but no SP-B positive cells were found in the lung tissues of CDH group fetal rats. After prenatal TET treatment,moderate ex-pression of SP-B was found in the lung tissues of TET group,and it was significantly lower than that of Control group (P 0.05). Compared with the other 2 groups,PCNA posi-tive cells in TET group were significantlydecreased (P < 0.01). Conclusions Prenatal tetrandrine (TET) treatment can accelerate fetal lung differentiation and maturation,and increase the expres-sion of SP-B in the hypoplastic lungs of the fetal rats with nitrofen-induced CDH. PCNA positive cells were decreased in the lung tissue of TET group rats,which indicates TET may not enhance lung mat-uration in CDH rat fetuses by increasing proliferation. Key words: Diaphragmatic hernia,Congenital; Pulmonary hypoplasia; Bronchopulmonary dys-plasia