| Part I: Comparison of effects of different prenataladministration of dexamethasone and ambroxol onpulmonary morphology of fetal and neonate rats[Abstract]Objective: To compare the effects of prenatal single-dose administration ofdexamethasone combined ambroxol and single-dose administration of dexamethasoneon pulmonary morphology of fetal and neonate rats.Methods: Fifty-four pregnant rats were randomly assigned to three groups: thedexamethasone group (n=18), the combination administration group (n=18) and thecontrol group (n=18). On the 17 day of pregnancy, the rats in the dexamethasonegroup were injected intraperitoneally with dexamethasone, the rats in the combinationadministration group were injected intraperitoneally with dexamethasone andambroxol while the rats in the control group were injected intraperitoneally withequivalent volumes of isotonic saline. The histologic structures of lungs of each groupwere observed with light microscope and trans-mission electron microscope on the 19day of pregnancy, postnatal 3 days and 7 days. The differences of pulmonarymorphogenesis among three groups on different periods were studied.Results: 1) Under the light microscope: on the 19 day of pregnancy, lungs in thetwo treatment groups had more alveolar numbers(P<0.05), larger alveolar space(P<0.01), and thinner alveolar septum(P1<0.05, P2<0.01)compared with the controlgroup, but between the two treatment groups there was no significant difference(P>0.05); on the postnatal 3 days, lungs in the combination administration group hadlarger alveolar space(P<0.05), thinner alveolar septum(P<0.05), while alveolarnumbers had no significant difference(P>0.05)compared with the control group, compared with the control group, the dexamethasone group lungs had no significantdifference of all the indicators(P>0.05); on the postnatal 7 days, lungs in thecombination administration group had larger alveolar space(P<0.05), thinner alveolarseptum(P<0.05), while alveolar numbers had no significant difference(P>0.05)compared with the control group, compared with the control group, lungs of thedexamethasone group had no significant difference of all the indicators(P>0.05). 2)Under the electronic microscope: villi of type II alveolar epithelial cells in the twotreatment groups were denser and more integral than those in the control group; thelamellar body could be seen in the two treatment groups while hardly in the controlgroup on the 19 day of pregnancy. There were many lamellar bodys in three groupswhile lamellar bodys in the combination administration group were moreanachromasis and condensed compared with the other two groups on the postnatal 3days and 7 days. There were also many cellular organs such as bioblast inendochylema of the combination administration group on the postnatal 3 days and 7days.Conclusion: Prenatal single-dose administration of dexamethasone can promotefetal lung maturation but had no obvious influence on neonate rats lung. Prenatalsingle-dose administration of dexamethasone and ambroxol can promote lungmaturation not only of fetal rats but also of neonate rats.Part II: Comparison of effects of different prenataladministration of dexamethasone and ambroxol onexpression of TLR4 and NF-κB of Fetal and Neonate Rats[Abstract] Objecti: To investigate the role of prenatal single-dose administration ofdexamethasone and ambroxol on the expression of toll-like receptor 4(TLR4) and NF-κB of fetal and neonate rats.Methods: Fifty-four pregnant rats were randomly divided into three groups witheighteen rats in each group: rats treated with dexamethasone, dexamethasone andambroxol, or saline(controls) on the 17th day of gestation. The lung tissues wereharvest independently on the 19th day of gestation, the postnatal 3 days and 7 days.The expressions of TLR4 and NF-κB of 6 fetal/neonatal rat lungs in each pregnant ratwere analyzed by reverse transcriptase polymerase chain reaction(RT-PCR),immunohistochemistry stain, and Western blotting.Results: 1) On the 19th day of pregnancy, TLR4 mRNA expression was upregulatedin lungs of the two treatment groups compared with controls(P1<0.05,P2<0.01). TLR4 mRNA expression was up-regulated in lungs of the combinationadministration group compared with controls on the postnatal 3 days and 7days(P<0.05), while no significant difference was found in the dexamethasone groupcompared with the controls(P>0.05). Results of the immunohistochemistry andWestern blotting demonstrated that: on the 19th day of pregnancy, the proteinexpression of TLR4 was significantly increased in the two treatment groups(P1<0.05,P2<0.01). The protein expression of TLR4 was significantly increased in lungs of thecombination administration group on the postnatal 3 days and 7 days(P<0.05), whileno notable difference could be found between the dexamethasone group and thecontrol group(P>0.05).2) NF-κB mRNA expression was significant up-regulated in the two treatment groupscompared with controls on the 19th day of pregnancy(P1<0.05, P2<0.01). On thepostnatal 3 days and 7 days, NF-κB mRNA expression was significant up-regulated inthe combination administration group compared with controls(P<0.05), while the change between the dexamethasone group and the control group was not significant(P>0.05). Results of Western blotting analysis manifested that the two treatmentgroups both had a higher NF-κB expression than that of the normal control on the 19thday of pregnancy(P1<0.05, P2<0.01). On the postnatal 3 days and 7 days, NF-κBexpression was significantly increased in lungs of the combination administrationgroup compared with controls(P<0.05), while no significant difference was found inthe dexamethasone group compared with the controls(P>0.05).Conclusion: Prenatal single-dose administration of Dexamethasone may upregulatethe expression of TLR4 and NF-κB in the rat fetal lung. The up-regulation ofTLR4 and NF-κB might be one of critical factors for the glucocorticoid-inducedmaturity of fetal lung. Prenatal single-dose administration of dexamethasone andambroxol may have effects on the regulation of TLR4 and NF-κB not only in the fetalrats but also in the neonate rats. |
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