Molecularbiological analysis of human fetal lung development and its clinical application

1. TTF-1是胎儿肺发育所必需的转录因子，我们分析了人TTF-1基因的顺式元件。TTF-1基因的肺选择性表达需要3 kb的TTF-15'区，HNF-3β在体外上调TTF-1基因的转录。在肺和脑中均检测到荧光素酶活性，这一发现表明3 kb的TTF-15'区不足以在体内进行肺特异性表达。我们报告一例双胞胎，其MRI上肺部信号强度有明显差异，这对预测胎儿的病理生理有帮助，宫内MRI使用SSFSE提供了产前诊断肺发育不良的可能性.当喂食妊娠小鼠至妊娠第9天时，除草醚（2，4-二氯苯-对-硝基苯醚）可导致胎仔肺发育不全，无生殖器官缺陷。腹腔注射全氟化碳导致肺扩张和延长 关于我们 d除草醚诱导的肺发育不良的存活率。全氟化碳可能有助于在治疗的早期阶段稳定肺发育不全婴儿的病情。我们评估了妊娠21周的人胎儿肺上皮细胞的成熟。免疫组化显示细支气管和终末气道均可见SP-B前体蛋白表达。而成熟的SP-B肽阳性细胞很少。透射电镜下可见胞内糖原颗粒丰富，板层体较少。这些发现意味着SP-B前原蛋白到成熟肽的加工在妊娠21周时是不成熟的。为了确定SP-B是否保护小鼠免受氧诱导的损伤，将杂合SP-B+/基因靶向小鼠和野生型SP-B+/+同窝小鼠暴露于高氧或室内空气。虽然SP-B+/小鼠在室内空气中的比肺顺应性与SP-B+/+小鼠相比略有降低，但在高氧时降低更明显。肺泡-毛细血管渗漏增加和SP-B相对缺乏可能导致SP-B+/小鼠氧诱导的肺功能障碍。这些数据支持SP-B在肺中起重要保护作用的概念。少

1. TTF-1 is a prerequisite transcription factor for intrauterine lung development, We analyzed cis-element of human TTF-1 gene. 3 kb of TTF-15' region is required for lung selective expression of TTF-1 gene, and HNF-3β upregulate TTF-1 gene transcription in vitro, We made 3 kb human TTF-1 promoted luciferase transgenic mice. Luciferase activity was detected in both lung and brain, This finding shows that 3 kb of TTF-15' region is not enough for lung specific expression in vivo,2. We presented a case of twin who showed a marked difference in signal intensity of the lung on MRI, which was useful for predicting the fetal pathophysiology, Intrauterine MRI using SSFSE provides the possibility of diagnosing hypoplastic lungs prenatally.3. Nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether) causes fetal lung hypoplasia without cingenital diaphragmatic defects, when fed to pregnant mice to Day 9 of gestation. Intratracheal administration of perfluorocarbon resulted in lung expansion and prolonge … More d survival of nitrofen induced lung hypoplasia. Perfluorocarbon may be useful in stabilizing critically in infants with pulmonary hypoplasia during the early phase of their therapy.4. We assessed maturation of pulmonary epithelial cells of human fetuses at 21 weeks of gestation. Immunohistochemical analysis showed SP-B proprotein was detected both bronchioles and terminal airways. However, mature SP-B peptide positive cells were very few. Transmission electron microscopy showed intracellular glycogen granules were still rich and lamellar bodies were few. These findings means the processing from SP-B preproprotein to mature peptide is immature at 21 weeks of gestation.5. To determine whether SP-B protects mice from oxygen-induced injury, heterozygous SP-B+/ gene-targeted mice and wild-type SP-B+/+ littermates were exposed to hyperoxia or room air. Although specific lung compliance in room air in SP-B+/ mice was slightly reduced as compared with that in SP-B+/+ mice, it was reduced more markedly during hyperoxia. Increased alveolar-capillary leakage and relative deficiency of SP-B may contribute to oxygen-induced pulmonary dysfunction in SP-B+/ mice. These data support the concept that SP-B plays an important protective role in the lung. Less