目的：探讨地塞米松与盐酸氨溴索对早产鼠肺组织中表面活性蛋白（surfactant protein，SP）-B mRNA及甲状腺转录因子（thyroid transcription factor，TTF）-1表达的影响及其作用机制。方法采用清洁级Sprague-Dawley大鼠，16只孕鼠随机分为4组，每组4只：地塞米松2剂组（分别于妊娠第17和18天肌内注射地塞米松0.2 mg/kg）、地塞米松1剂组（妊娠第18天肌内注射地塞米松0.2 mg/kg）、盐酸氨溴索组（分别于妊娠第16、17和18天腹腔注射盐酸氨溴索100 mg/kg）、对照组（分别于妊娠第16、17和18天腹腔注射生理盐水）。4组孕鼠均于妊娠第19天剖宫产取出胎鼠制成早产鼠模型，每组早产鼠中随机选择20只作为研究对象。计算肺重与体重的比值，光镜下观察肺形态发育，并计算肺泡腔表面积与肺泡间隔表面积的比值。采用免疫组织化学检测TTF-1蛋白表达。采用逆转录聚合酶链反应技术检测SP-B mRNA表达。统计学方法采用单因素方差分析、Student-Newman-Keuls法、Pearson积差相关分析。结果（1）地塞米松2剂组、地塞米松1剂组、盐酸氨溴索组和对照组肺重与体重的比值分别为（6.5±0.6）、（7.9±0.8）、（9.5±0.8）与（9.5±0.9） mg/g，4组间比较差异有统计学意义（F=67.69，P<0.01）；地塞米松2剂组和1剂组均低于对照组（q值分别为17.143和9.143，P值均<0.01）及盐酸氨溴索组（q值分别为17.143和9.143，P值均<0.01）；地塞米松2剂组低于1剂组（q=8.000，P<0.01）。（2）地塞米松2剂组、地塞米松1剂组、盐酸氨溴索组和对照组肺泡腔表面积与肺泡间隔表面积的比值分别为2.19±0.15、1.70±0.18、1.67±0.13与1.08±0.12，4组间比较差异有统计学意义（F=190.85，P<0.01）；地塞米松2剂组、地塞米松1剂组和盐酸氨溴索组均高于对照组（q值分别为33.639、18.788和17.879，P值均<0.01）；地塞米松2剂组高于1剂组（q=14.848，P<0.01）。（3）地塞米松2剂组、地塞米松1剂组、盐酸氨溴索组和对照组肺组织TTF-1蛋白表达分别为0.311±0.018、0.224±0.019、0.196±0.013与0.191±0.018，4组间比较差异有统计学意义（F=211.69，P<0.01）；地塞米松2剂组和1剂组均高于对照组（q值分别为30.000和8.250，P值均<0.01）和盐酸氨溴索组（q值分别为28.750和7.000，P<0.01）。地塞米松2剂组高于地塞米松1剂组（q=21.750，P<0.01）。（4）地塞米松2剂组、地塞米松1剂组、盐酸氨溴索组和对照组肺组织SP-B mRNA表达分别为1.25±0.13、1.15±0.12、1.10±0.10与1.01±0.12，4组间比较差异有统计学意义（F=14.48，P<0.01）；地塞米松2剂组、地塞米松1剂组和盐酸氨溴索组均高于对照组（q值分别为9.231、5.385和3.462，P值均<0.01）；地塞米松2剂组高于盐酸氨溴索组（q=5.769，P<0.01）和地塞米松1剂组（q=3.846， P<0.01）。（5）地塞米松2剂组、地塞米松1剂组、对照组的TTF-1表达和SP-B mRNA表达呈正相关（r值分别为0.512、0.597、0.449，P值均<0.05）。结论盐酸氨溴索具有促进肺组织发育成熟的作用，且对肺重与体重的比值无明显影响，有可能替代糖皮质激素用于预防新生儿呼吸窘迫综合征。%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.
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