| Glucocorticoids (GC) can enhance the fetal lung development. On the other hand, various clinical trials have discovered that GC is associated with aggravating infection, increasing sepsis and retarding fetal growth . When treating preterm premature rupture of membranes, GC can not reduce the frequency of respiratory distress syndrome (RDS). However, there are not other more effective drugs found.Previous studies have demonstrated that thyrotropin releasing hormone (TRH) can pass through placenta from maternal to the fetal bloodstream and cause an increase of thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxin (74) and prolactin, which promote the fetal lung maturation. TRH can accelerate the morphogenesis of fetal lung. TRH combination with Dex can result in an increase of the lecithin to sphingomyelin ratio and a decrease of frequency of RDS in preterm newborn. Epidermal growth factor (EGF) is known to stimulate cell mitogenesis and maturation in a variety of tissues. Experemental studies have shown that EGF can promote the morphological development and the histologic maturation of hypoplastic fetal murine lungs. EGF increase the levels of aminopeptidase N mRNA in fetal rat lung in vitro. The fetal rhesus monkeys exposed prenatally to EGF have less frequent RDS. All these data suggest that TRH and EGF will be expected as fetal lung maturation improving drugs in future. However, their effects and the mechanisms improving lung maturation are not quite clear. The effects of TRHand EGF on the surfactant protein mRNA expression have not been demonstrated. In addition, there was no direct comparison of the effects of EGF, TRH and Dex on lung maturation in vivo, and the different effects of these hormones on fetal lung development and maternal-fetal outcomes in the model of infection have not been known.The purpose of the study is to compare the effects of maternal treatment with EGF, TRH and Dexamethasone on the morphological and functional development of immature fetal lung and pregnancy outcomes in rabbits in vivo, thus further to explore the effect mechanism and discuss the safety of EGF, TRH and Dex on mother and their fetuses. The results of this study are as follows.1. Comparison of the effects of maternal treatment with TRH, EGF and Dex on immature fetal lung morphogenesis.In order to evaluate the difference of EGF, TRH and Dex in stimulating fetal lung development and the effect of gestational age on the their efficacy, we compared the effects of maternal treatment with EGF, TRH and Dex between 24 and 26 days or 22 and 24 days of gestation on the morphogenesis and the type II cell differentiation of fetal lung. Larger and more uniform alveolar air spaces in size with thinner alveolar septa were found in 27 day lung from EGF, TRH and Dex treated groups when compared with the control group. No difference was found among these three treated groups. The alveolar air spaces in 25 day fetal lung from EGF, TRH and Dex treated groups were larger than that of control group, but the effect of Dex was more marked than EGF and TRH groups. The ultrastructural features of alveolar type II cells in EGF, TRH and Dex treated rabbits in 27 day gestation differed from that of control rabbits. Alveolar type II cells in each treatment group contained more lamellar bodies and less glycogen as compared with that of the control group , but no apparent difference amongthese treated groups. However, only few type II cell between Dex-treated group contained less and small, if any, lamellar bodies in 25 day lung . In contrast to lamellar body, glycogen was very abundant in every groups.2. Regulation of EGF, TRH and Dex on expression of SP mRNAs. Previous studies suggested that Dex can up-regulate or down- regulate theexpression of on SP mRNAs in fetal lung, which is affected by other factors. However, the effects of EGF and TRH on SP mRNAs levels are not clear. Our aims are to compare the regulations of EGF, TRH and Dex on the levels of SP-A, SP-B and SP-C mRNA in fe...
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