Stahlman M T, Gray M E, Chytil F, Sundell H
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Lab Invest. 1988 Jul;59(1):25-35.
Twelve pairs of fetal lambs were used to test the hypothesis that the necrotizing tracheobronchitis followed by squamous metaplasia seen in premature infants who develop chronic bronchopulmonary dysplasia might be related to low retinol stores and might, therefore, be reversed by retinol supplementation. Epidermal growth factor (EGF) was used to model the growth factor stimulus initiated by chronic wounding of the airways, and retinol was used as a differentiator of proliferating cells stimulated by EGF. Saline-treated animals were used as controls, as were fetal lambs receiving retinol alone or EGF alone. The effects of EGF on tracheal and bronchial epithelium consisted of proliferation of basal and intermediate cells, necrosis and slough of lining ciliated and mucous-producing cells, followed by squamous metaplasia. In fetal lambs given retinol, plasma, liver and lung retinol levels rose and mucous producing cells were increased in number. In the presence of EGF plus retinol, differentiation of mucous-producing cells was accelerated. We believe that this fetal lamb model with low initial levels of retinol in plasma, liver and lung, treated with EGF may mimic human premature infants with chronic bronchopulmonary dysplasia, and that the addition of retinol in amounts sufficient to raise their tissue levels produces a more normal surface epithelium in conducting airways.
使用12对胎羊来检验以下假设：在患慢性支气管肺发育不良的早产儿中出现的坏死性气管支气管炎继以鳞状化生，可能与视黄醇储备低有关，因此可能通过补充视黄醇得到逆转。表皮生长因子（EGF）被用于模拟由气道慢性损伤引发的生长因子刺激，视黄醇被用作受EGF刺激的增殖细胞的分化剂。用盐水处理的动物用作对照，单独接受视黄醇或单独接受EGF的胎羊也用作对照。EGF对气管和支气管上皮的影响包括基底细胞和中间细胞的增殖、衬里的纤毛细胞和黏液分泌细胞的坏死和脱落，继以鳞状化生。给予视黄醇的胎羊，其血浆、肝脏和肺中的视黄醇水平升高，黏液分泌细胞数量增加。在EGF加视黄醇的情况下，黏液分泌细胞的分化加速。我们认为，这种血浆、肝脏和肺中视黄醇初始水平低且用EGF处理的胎羊模型可能模拟患慢性支气管肺发育不良的人类早产儿，并且补充足以提高其组织水平的视黄醇会使传导气道的表面上皮更接近正常。
