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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 investigate the regulation of cytokines on the development, differentiation and maturation of alveolar type Ⅱ cells. Methods Totally 13 lung tissues from 12 to 35 weeks were embedded in paraffin and paraffin embedded. The expression of FGFR, Ras p21, BMP 4, SP B and TTF 1 were detected by immunohistochemistry. Results FGFR was first expressed in proximal bronchial epithelium during early development. Ras protein was weaker in the proximal and distal bronchial epithelium at 16 weeks, and peaked at 18 weeks as FGFR. As FGFR expression increases, BMP 4 begins to express. Late development, these three are not expressed. TTF 1 locates in the nucleus of epithelial cells from the 16th week. The response of the distal bronchus is always stronger than that of the proximal end. SP B protein appeared in type II alveolar cells of fetal lungs at 18 weeks. With the expression of TTF 1, the reaction gradually migrated from the proximal respiratory tract to the distal end. From the end of development to the formation of lung, the positive reaction of TTF 1 and SP B was stably expressed in type Ⅱ alveolar cells. Conclusion The effect of FGF 10, Ras protein and BMP 4 on type Ⅱ alveolar cells promotes the normal proliferation and differentiation of type Ⅱ alveolar cells and the maturation of morphology through the extracellular matrix pathway. The expression of TTF 1 and SP B, Type Ⅱ alveolar cells in the early stages of fetal lung development has gradually reached the mark of functional maturity, and the birth of a fetus that has the function of spontaneous breathing adapted.