Effect And Significance Of Tetrandrine On The Expression Of VEGF In The Fetal Lung Of Rat Models With CDH

[Objective] To research the expression and significance of VEGF in pulmonary hypoplasia in fetal rat lung with congenital diaphragmatic hernia(CDH) and evaluate the effect of intervention by Tetrandrine in fetal lung development of rat with CDH.[Meterials and Methods] Pregant Sprague-Dawley rats were divided into 3 groups: group 1. Normal Control(NC group); group 2. Congenital Diaphragmatic Hernia(CDH group); group 3. Congenital Diaphragmatic Hernia Tetrandrine(CDH TET group); Each pregant rat in group 1 was administered olive oil 2ml by gavage on day 9.5 of gestation. Other groups rats were administered a single oral dose 125mg/rat of Nitrofen. From day 11 of pregnancy, Tetrandrine 30mg/kg/d was administered by gavage to each rat in group 3 for three days. NS 2ml was administered by gavage to each rat in the others for three days. The pregnant rats were anesthetized with ether on day 16, 18 and 21 of gestation respectively, then the fetuses were delivered by cesarean section and executed by decollation. The lung tissue was observed under the optical microscope and the transmission electron microscope to valuate the histological feature of lung. FⅧwere assayed by immunohistochemistry and VEGF were tested by in-situ hybridization. The expression and significance of FⅧand VEGF in the fetal lung tissue was analyzed with orientation and quantitation. The data were analyzed by statistic.[Results] The ratio of the fetuses with CDH of the fetuses in the group 2 and 3 was 85％and 77％respectively, there was no any CDH fetus in group 1 on 18-day and 21-day gestation. The ratio of CDH fetuses in group2 and 3 on 18day and 21day had no difference in statistic(P＞0.05). It is observed under the optical microscope and the transmission electron microscope that there were reduced external diameter or increased medial wall thickness of prealveolar vessel,decreased number of intra-alveolar vessel and increased thickness of alveolocapillary barrier in the fetal lung of group 2. compared with group 1, All of those process reverted in group 3 for the administration of TET. The expression of FⅧwas more obvious in group 1 than in group 2. The expression of FⅧin group 3 was more close to the group 1. There was significant difference between the number of capillary vessel which was marked by FⅧof group 2 and group 1, and the same in the group 2 and group 3(P＜0.05). But there was on significant difference between group 1 and group 3(P=0.33). There were no significant difference the number of expression of VEGFmRNA in group 1,2 and 3(P＞0.05). But there were some difference among those three groups with regard to the domain of VEGFmRNA expression. In group 3, the expression of VEGFmRNA was decreased within the domain of intra-alveolar vessel and increased within the domain of prealveolar vessel. This phenomenon was reverted in group 3.[Conclusions]1. The teratogen Nitrofen can produces a congenital diaphragmatic hernia (CDH) with pulmonary hypoplasia in rodent fetuses that closely parallel observations made in humans. The most of the diaphragmatic hernia exist at left for prenatal intervention Nitrofen on day 9.5 of gestation.2. In the Nitrofen model rat, the pulmonary vascular bed is decreased significantly because of the increased medial wall thickness of prealveolar vessel and decreased number of intra-alveolar vessel. Those process can be reverted by TET.3. TET can decrease the thickness of alveolocapillary barrier in the fetal lung of CDH rat. This may elevate the saturation of blood oxygen in postnatal.4. The relationship between CDH and VEGF is still not clear. It remains a long way to declare the mechanism of the role of VEGF in CDH..