The effects of prenatal tetrandrine treatment on pulmonary vascular development and CTGF expression in rats with congenital diaphragmatic hernia

Objective To explore the effects of prenatal tetrandrine treatment on vascular devel opment and CTGF expression in the lungs of rats with congenital diaphragmatic hernia (CDH) induced by Nitrofen.Methods Nine pregnant Sprague-Dawley rats were randomly and evenly divided into 3 groups according the treatment:C group (control group),NT group (tetrandrine group) and N group (nitrofen group).The rats of the N and NT group were administrated with 125 mg of nitrofen dissolved in 2 ml of olive oil by gastric gavage on day 9.5 of gestation,whereas those in C group only received same volume of olive oil.The rats of the NT group were administered with Tet (30 mg/kg)once a day from gestational day 18.5 to 20.5,while their counterparts of the C and N group were only treated with saline.On day 21 of gestation,all fetuses were delivered by cesarean section.The rat fetuses were sacrificed and examined for diaphragmatic hernia.Lung vascular dysplasia or remodeling was evaluated on H&E staining slides.Immunohistochcmical staining and real time polymerase chain reaction (RT-PCR) were performed to detect the expression of CTGF in lung tissues.Results Twenty-seven (50％) fetuses with CDH were harvested from the N and NT rats.No significant difference of CDH incidence was seen between the two groups (P＞0.5).More pulmonary vessels were observed in the fetuses of C group,and these vessels had thinner medial smooth muscle and adventitia,and larger lumina compared with the counterparts of N and NT group.The pulmonary vascular development of the fetuses of NT group was better than that of the N group.There were significant differences between the C and the other two groups in internal diameter (ID) (P＜0.01) and percentage of adventitial thickness (AT％) (P＜0.01).The ID of N group was smaller than that in the other 2 groups (P＜0.01),but the medial thickness (MT％) and AT％ of N group were larger than those in the other 2 groups (P＜0.01).The highest protein and mRNA expression of CTGF were observed in N group,followed by NT group and C group (P＜0.01).Conclusions Prenatal treatment with tet randrine can promote lung development and inhibit pulmonary arterial structural remodeling in fetal rats with nitrofen-induced CDH via the unregulated expression of CTGF in the lungs. Key words: Hernia,Diaphragmatic; Connective tissue growth factor; Rats