胎鼠气管阻塞改变间充质核转录因子的表达，而不影响表面活性物质蛋白的表达。

Tracheal occlusion in fetal rats alters expression of mesenchymal nuclear transcription factors without affecting surfactant protein expression.

作者信息

Danzer Enrico, Robinson Lauren E, Davey Marcus G, Schwarz Uwe, Volpe MaryAnn, Adzick N Scott, Flake Alan W, Hedrick Holly L

机构信息

The Children's Institute for Surgical Science, Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4318, USA.

出版信息

J Pediatr Surg. 2006 Apr;41(4):774-80. doi: 10.1016/j.jpedsurg.2006.02.026.

DOI:10.1016/j.jpedsurg.2006.02.026

PMID:16567192

Abstract

BACKGROUND/PURPOSE: Mesenchymal nuclear transcription factors (MNTF) are involved in lung development and maturation and regulate surfactant protein (SP) expression. Prolonged (>2 weeks) fetal tracheal occlusion (TO) has been shown to accelerate lung growth and inhibit pulmonary surfactant synthesis. The effects of TO on SP expression and MNTF, however, have not been formally assessed. The objectives of this study were to evaluate the effects of short-term (3 days) TO on normal lung growth and protein expression of pulmonary MNTF involved in SP synthesis.

METHODS

At E19 (term, 22 days), 2 fetuses per time-dated Sprague-Dawley rats underwent either TO (n = 23) or a sham (n = 22) operation. Lungs were harvested 72 hours post surgery. Pulmonary SP-A; SP-B; SP-C messenger RNA (mRNA) expression; and SP-A and SP-B, Hoxb5, thyroid transcription factor 1, and retinoic X receptor-alpha protein expression were analyzed.

RESULTS

Lung weight was significantly increased by TO (TO 0.32 +/- 0.02g vs SHAM 0.14 +/- 0.01 g; P < .001), resulting in 123% increase of the lung-to-body-weight ratio. No difference of SP-A-mRNA (177 +/- 4.3 TO vs 169 +/- 4.4 SHAM; P = .25), SP-B-mRNA (87.7 +/- 0.2 TO vs 87.4 +/- 0.02 SHAM; P = .33), and SP-C-mRNA (186.5 +/- 3.2 TO vs 183.2 +/- 2.7 SHAM; P = .45) expression was found. Surfactant protein A (175.6 +/- 25.3 TO vs 192.5 +/- 19.8 SHAM; P = .59) and SP-B (163.4 +/- 5.2 TO vs 166.8 +/- 9.3 SHAM; P = .75) protein expression were similar in both groups; however, Hoxb5 (70.3 +/- 18.9 TO vs 130.6 +/- 5.1 SHAM; P = .02) and thyroid transcription factor 1 (102.6 +/- 19 TO vs 181.1 +/- 6.3 SHAM; P = .007) expression were significantly decreased. Retinoic X receptor-alpha expression tended to be increased by TO (171.9 +/- 6.0 TO vs 155.4 +/- 6.7 SHAM; P = .06).

CONCLUSIONS

Short-term TO late in gestation induces rapid lung growth. Surfactant protein-mRNA and protein expression are not significantly altered. Thyroid transcription factor 1 and Hoxb5 are down-regulated by TO, suggesting that duration and timing of occlusion are important in balancing the effects of TO on lung growth vs lung maturation.

摘要

背景/目的：间充质核转录因子（MNTF）参与肺的发育和成熟，并调节表面活性物质蛋白（SP）的表达。已表明延长（>2周）胎儿气管阻塞（TO）可加速肺生长并抑制肺表面活性物质的合成。然而，TO对SP表达和MNTF的影响尚未得到正式评估。本研究的目的是评估短期（3天）TO对正常肺生长以及参与SP合成的肺MNTF蛋白表达的影响。

方法

在胚胎第19天（足月为22天），对每只按时间记录的Sprague-Dawley大鼠的2只胎儿进行TO手术（n = 23）或假手术（n = 22）。术后72小时收获肺组织。分析肺组织中SP-A、SP-B、SP-C信使核糖核酸（mRNA）表达，以及SP-A和SP-B、Hoxb5、甲状腺转录因子1和视黄酸X受体α蛋白表达。

结果

TO使肺重量显著增加（TO组0.32±0.02g，假手术组0.14±0.01g；P <.001），导致肺与体重之比增加123%。SP-A-mRNA（TO组177±4.3，假手术组169±4.4；P =.25）、SP-B-mRNA（TO组87.7±0.2，假手术组87.4±0.02；P =.33）和SP-C-mRNA（TO组186.5±3.2，假手术组183.2±2.7；P =.45）表达无差异。两组表面活性物质蛋白A（TO组175.6±25.3，假手术组192.5±19.8；P =.59）和SP-B（TO组163.4±5.2，假手术组166.8±9.3；P =.75）蛋白表达相似；然而，Hoxb5（TO组70.3±18.9，假手术组130.6±5.1；P =.02）和甲状腺转录因子1（TO组102.6±19，假手术组181.1±6.3；P =.007）表达显著降低。视黄酸X受体α表达有被TO增加的趋势（TO组171.9±6.0，假手术组155.4±6.7；P =.06）。