中文摘要：

目的探讨缺氧诱导丝裂原因子（hypoxia-induced mitogenic factor，HIMF）对胎肺形态发育及表面活性蛋白B（surfactant proteinB，SP-B）、表面活性蛋白C（surfactant proteinC，SP-C）表达的调控作用。方法体外分离、培养小鼠第13．5天胎肺组织，分为HIMF处理组：在培养基中添加重组HIMF蛋白，终浓度为100nmol／L；对照组培养基中不加任何处理。分别在培养0、48、72h后，每组每时间点选取20例胎肺采用倒置显微镜和HE染色观察胎肺形态学和组织学的改变，采用Western印迹、免疫组化、实时逆转录-聚合酶链反应技术检测胎肺组织中SP-B和SP-C的蛋白、mRNA表达水平变化。结果HIMF处理组培养48、72h后，肺泡数目分别为（14．37±0．85）和（18．41±1．24）个／高倍视野，肺泡分支的数目分别为（2．51±0．35）和（3．28±0．51）个／高倍视野，均较对照组相应时间点[分别为（8．09±0．92）、（9．54±0．78）、（1．45±0．32）和（1．69±0．43）个／高倍视野]增加，差异有统计学意义（P〈0．05）。对照组胎肺体外培养72h后，SP—B、SP—C蛋白表达较少，染色强度弱，主要定位于Ⅱ型肺泡上皮细胞；HIMF处理组可见Ⅱ型肺泡上皮细胞内SP-B、SP-C弥漫表达，以靠近肺组织边缘为甚。HIMF处理组培养48和72h后，胎肺组织中SP-B、SP-C蛋白和mRNA水平均较对照组相应时间点增加，差异有统计学意义（P〈0．05）。结论HIMF可能通过上调胚胎组织中SP-B和SP-C的表达，促进胎肺形态发育，为进一步研究HIMF在胚胎肺泡发育和成熟中的作用奠定了基础。

英文摘要：

Objective To explore the regulatory effects of hypoxia-induced mitogenic factor （HIMF） on lung morphogenesis and expression of surfactant protein B （SP-B） and surfactant protein C （SP-C） in embryonic lungs of mouse. Methods The mouse lungs at embryonic day 13.5 were separated and cultured in vitro, and divided into HIMF treatment group with final concentration as 100 nmol/L and control group with no HIMF. After incubation for 0, 48 and 72 hours, cultured embryonic lungs from each group were harvested for HE staining-mediated morphological observation. The changes of SP-B and SP-C expression in embryonic lungs were explored by western blot, immunohistochemical staining and real-time RT-PCR. Resells Administration of HIMF for 48 and 72 hours, morphogenesis were （14.37±0.85）and（18. 41± 1.24）/HP, and branching of the buds were （2.51±0. 35） and （3.28±0. 51）/HP, higher than those at the relative time points in control group, which were （8. 09±0.92） ,（9.54±0.78） ,（1.45±0.32） and （1.69±0. 43）/HP, respectively （P〈0.05）. In control embryonic lungs cultured for 72 hours, the expression of SP-B and SP-C was reduced, mainly locating at type Ⅱ lung epithelial cells. Within the HIMF-treated embryonic lungs, there were intensive and diffuse expression of SP-B and SP-C, mainly around the edge of lung tissues. Compared with controls, the levels of SP-B protein and rnRNA, SP-C protein and rnRNA within HIMF-treated embryonic lungs for 48 and 72 hours were increased （P〈0.05）. Conclusions HIMF may promote lung morphogenesis via enhancing the expression of SP-B and SP-C in cultured embryonic lungs, which establishes a basis for further studying the roles of HIMF in lung alveolar development and maturation.