角质细胞生长因子对高氧暴露下新生大鼠SP-A表达的影响

Effect of keratinocyte growth factor on the expression of surfactant protein A in newborn rats exposed to high oxygen

目的研究角质细胞生长因子(KGF)对高氧暴露下新生大鼠肺组织SP-A表达的影响。方法将生后3d的54只SD大鼠随机分为三组。A组:空气组,B组:高氧组,C组:KGF干预组。B、C组大鼠持续暴露于95%氧气中,C组于吸氧同时于背部皮下注射htKGF1mg/kg/d,连用3d后改为0.5mg/kg/d直至实验结束。A组和B组给予等量生理盐水。A组大鼠呼吸空气。于高氧暴露后3d、7d、14d取肺组织,采用免疫组化方法观察肺组织中SP-A表达的变化。结果B组高氧暴露3d时SP-A表达强度较A组增强(P<0.05);高氧暴露7d时SP-A表达强度与A组相比较,差异无统计学意义(P>0.05),高氧暴露14d时SP-A表达强度较A组和KGF组减弱,差异有统计学意义(P<0.01)。SP-A在C组与A组在3d、7d、14d的表达无显著性差异。结论长时间暴露于高氧环境,使肺泡Ⅱ型上皮细胞(AECⅡ)受损,SP-A分泌随之减少,导致PS功能丧失,阻碍肺发育,KGF促进AECⅡ增殖和分化,增加肺表面活性物质合成与分泌,对胎肺的发育和分化具有重要作用。

Objective To explore the effect of keratinocyte growth factor （KGF） on expression of surfactant protein A （SP-A） in lung tissues of newborn rats exposed to high oxygen. Methods There 54 SD rats 3 days after birth were randomly divided into three groups including air group （group A）, high-oxygen group （group B） and KGF intervention group （group C）. Rats in groups B and C were continually exposed to 95% oxygen,rats in group C wer exposed to oxygen and at the same time intramuscularly given htKGFlmg/kg.d in the back continuously for thee days then with 0.5mg/kg.d until the end of the experiment.Rats in group A and B were given normal saline. Rats in group A breathed air. Lung tissues were collected 3,7 and 14 days after exposed to high oxygen. The expression of SP-A in lung tissues was determined with immunochemistry. Results The expression of SP-A in group B 3 days after exposed to high oxygen was increased compared with the that of group A （P〈0.05）;The intensity of expression of SP-A in rats of group B 7 days after exposed to high oxygen was similar with that group A （P〉0.05） ,while the expression of SP-A became weak 14 days after exposed to high oxygen compared with that of KGF group,showing statistically significance （P〈0.01） .The expression of SP-A was not significantly differente in group C and A 3 days,7 days and 14 days after exposure. Conclusion The prolonged exposure to high oxygen the secretion of SP-A would reduced due to damage to alveolar epithelial type II cells （AEC II ） ,resulting in the loss of PS function, impeding lung development. KGF can promote the proliferation and differentiation of AEC II , enhance pulmonary surfactant synthesis and secretion, thus it plays an important role in fetal lung development and differentiation.