Effects of antenatal dexamethasone and ambroxol on expression of surfactant protein-B mRNA and ;thyroid transcription factor-1 in pulmonary tissue of premature rats / 中华围产医学杂志

ABSTRACT

To explore the effects and mechanism of dexamethasone and ambroxol on expression of surfactant protein (SP)-B mRNA and thyroid transcription factor (TTF)-1 in premature rat lung. Methods Sixteen pregnant Sprague-Dawley rats were randomly divided into four equal groups two doses of dexamethasone (0.2 mg/kg injected intramuscularly on Day 17 and 18 of pregnancy respectively);single dose of dexamethasone (0.2 mg/kg injected intramuscularly on Day 18 of pregnancy);ambroxol group (100 mg/kg injected intraperitoneally on Day 16, 17 and 18 of pregnancy respectively); and control group (normal saline injected intraperitoneally on Day 16, 17 and 18 of pregnancy respectively). There were four pregnant rats in each group. All of the fetal rats were taken out on Day 19 of pregnancy as the preterm birth model, and 20 fetal rats from each group were randomly selected. The ratio of body weight to fetal lung weight of newborn rats was calculated. Changes in lung morphology were observed under light microscopy and the ratio of alveoli surface area to alveolar septae surface area was calculated. Expression of TTF-1 protein was determined by immunohistochemistry. Expression of SP-B mRNA was detected by reverse transcriptase-polymerase chain reaction. One-way analysis of variance, Student-Newman-Keuls method and Pearson correlation analysis were applied as statistical methods. Results (1) The ratio of body weight to fetal lung weight was (6.5±0.6), (7.9±0.8), (9.5±0.8) and (9.5±0.9) mg/g in two doses of dexamethasone group, one dose of dexamethasone group, ambroxol group and control group respectively (F=67.69,P<0.01). The ratio of two doses and one dose of dexamethasone group was lower than that of control group (q=17.143 and 9.143, all P<0.01) and ambroxol group (q=17.143 and 9.143, all P<0.01). The ratio of two doses dexamethasone group was lower than that of one dose dexamethasone group (q=8.000, P<0.01). (2) The ratio of alveoli surface area to alveolar septae surface area was 2.19±0.15, 1.70±0.18, 1.67±0.13 and 1.08±0.12 in two doses of dexamethasone group, one dose of dexamethasone group, ambroxol group and control group respectively (F=190.85, P<0.01). The ratio of two doses of dexamethasone group, one dose of dexamethasone group and ambroxol group were higher than that of the control group (q=33.639, 18.788 and 17.879, all P<0.01). The ratio of two doses dexamethasone group was higher than that of one dose dexamethasone group (q=14.848, P<0.01). (3) Expression of TTF-1 protein was 0.311±0.018, 0.224±0.019, 0.196±0.013 and 0.191±0.018 in two doses of dexamethasone group, one dose of dexamethasone group, ambroxol group and control group respectively (F=211.69,P<0.01). TTF-1 protein expression of two doses and one dose of dexamethasone group were higher than that of control group (q=30.000 and 8.250, all P<0.01) and ambroxol group (q=28.750 and 7.000, all P<0.01). TTF-1 protein expression of two doses dexamethasone group was higher than that of one dose dexamethasone group (q=21.750, P<0.01). (4) Expression of SP-B mRNA was 1.25±0.13, 1.15±0.12, 1.10±0.10 and 1.01±0.12 in two doses of dexamethasone group, one dose of dexamethasone group, ambroxol group and control group respectively (F=14.48, P<0.01). SP-B mRNA expression of two doses of dexamethasone group, one dose of dexamethasone group and ambroxol group were higher than that of control group (q=9.231, 5.385 and 3.462, all P<0.01). SP-B mRNA expression of two doses of dexamethasone group was higher than that of ambroxol group (q=5.769, P<0.01) and one dose of dexamethasone group (q=3.846, P<0.01). (5)TTF-1 expression in two doses of dexamethasone group, one dose of dexamethasone group and control groups was positively correlated with SP-B mRNA expression (r=0.512, 0.597 and 0.449, respectively, all P<0.05). Conclusions Ambroxol can accelerate the maturation of fetal lung with minimal adverse effects on fetal lung weight. Ambroxol might be an alternative to dexamethasone to prevent neonatal respiratory distress syndrome.