胎儿肺Ⅱ型肺泡细胞发育中相关活性物质的表达及其意义

EXPRESSION OF INTERRELATED POLYPEPTIDES AND THEIR REGULATIVE FUNCTION IN TYPE Ⅱ ALVEOLAR CELLS OF FETAL LUNGS

目的 探讨诸细胞因子对肺泡Ⅱ型细胞发育、分化和成熟的调控作用。 方法 12～35周胎儿肺组 织共13例,常规石蜡包埋、切片,用免疫组织化学技术检测FGFR、Ras p21蛋白、BMP 4、SP B和TTF 1的表达特征。 结果 FGFR率先在发育早期近端支气管上皮表达。Ras蛋白于16周在近端和远端的支气管上皮有较弱表达,18 周时与FGFR一样达到表达的高峰。随着FGFR表达的增强,BMP 4开始表达。发育后期,这三者均不表达。TTF 1 因子自16周起定位于上皮细胞核内,远端支气管的反应总是较近端者强。SP B蛋白在18周胎儿肺Ⅱ型肺泡细胞 内出现,伴随着TTF 1的表达,其反应由呼吸道近端逐渐往远端迁移。发育末期至成肺中,TTF 1和SP B阳性反应 均在肺泡Ⅱ型细胞中稳定表达。 结论 FGF 10、Ras蛋白和BMP 4对Ⅱ型肺泡细胞的作用,是通过细胞外间质的 途径促使Ⅱ型肺泡细胞正常增殖分化和达到形态结构的成熟;而TTF 1因子和SP B的表达,则为Ⅱ型肺泡细胞在 胎肺发育晚期已逐渐达到功能成熟的标志,与胎儿一出生即具有自主呼吸的功能相适应。

Objective To observe the distributions of fibroblast growth factor-10(FGF-10), ras protein (Ras-p21),bone morphogenetic protein-4(BMP-4), surfactant protein-b and thyroid transcription factor-1 (TTF-1) in fetal lungs,and to discuss their function and their interaction. Methods Thirteen specimens of fetal lungs (from the 12th week to the 35th week of gestation) were obtained. The expression of 5 kinds of polypeptides (FGFR, BMP-4, Ras protein,SP-B,TTF-1) were examined by immunohistochemistry and re-stained by SP method. Results FGFR first localized in the airway surface epithelium during early lung (at the 12th week) development.Its staining in distal bronchiolar epithelial cells is always more intense than that in proximal ones. at the 16th week, Ras-p21 protein was detected in distal and proximal epithelial cells and reached its highest lever with FGFR at the 18th week. In this stage, the staining of BMP-4 is more obvious in airway epithelium. The main function of BMP-4 is to restrain the expression of FGF-10 which mainly expressed in mesenchyme. Furthermore, in the late stage of development, these three factors all have no active reaction in the fetal lungs. TTF-1 was expressed throughout fetal lung development from the 16th week.TTF-1 was prominent in the nuclei of distal lung buds, which was more intense than any of airway epithelium. But SP-B was expressed in cytoplasm from the 18th week. The positive reaction of SP-B in distal airway epithelium was more intense than that in proximal ones. From the 25th week to newborn and the adult, the stable expressions of TTF-1 and SP-B were both in the cytoplasm of type Ⅱ alveolar cells. Conclusion FGF-10,Ras-p21 and BMP-4 mainly accelerate proliferation and differentiation of the type Ⅱ alveolar cells, and make them more mature in morphology;TTF-1 and SP-B mainly make them mature in function and suitable for respiration.