脂肪型脂肪酸结合蛋白在早产大鼠高氧肺损伤时的表达

Increased expression of fatty acid binding protein 4 in lungs of preterm rats after hyperoxic lung injury

目的观察脂肪型脂肪酸结合蛋白4(FABP4)在早产大鼠高氧肺损伤时肺组织及支气管肺泡灌洗液(BALF)中的表达,探讨其与新型支气管肺发育不良(BPD)发病机制之间的关系。方法早产大鼠生后6 h内随机分为高氧组和对照组,对照组置于常压空气中,高氧组置于浓度为60%的高氧舱中,两组均于出生后第3天(P3)、第7天(P7)和第14天(P14)各随机取8只大鼠,采用免疫组织化学方法和逆转录-聚合酶链反应技术检测不同时间两组肺组织FABP4蛋白及mRNA表达水平,应用ELISA方法检测BALF中FABP4的含量。结果 FABP4主要在肺泡巨噬细胞、支气管上皮细胞和血管内皮细胞表达。两组FABP4蛋白和mRNA在肺组织中的表达以及两组BALF中FABP4的含量均随鼠龄递增呈逐渐增加的趋势,至P14时最高。高氧组肺组织中FABP4 mRNA的表达在P7、P14,FABP4蛋白的表达在P3、P7及P14时均高于对照组(均P<0.05);高氧组BALF中FABP4的含量在P7、P14时均高于对照组(均P<0.05)。结论高氧肺损伤时FABP4表达升高,可能是引起肺微血管发育障碍及肺泡化进程受阻,进而导致新型BPD发生的重要因素。

Objective To study the expression of fatty acid binding protein 4 （FABP4） in lungs and bronchoalveolar lavage lfuid （BALF） of preterm rats exposed to 60%O2 and to elucidate the relationship between the changes of FABP4 expression and the pathogenesis of bronchopulmonary dysplasia （BPD）. Methods Hyperoxic lung injury was induced by exposing to 60% O2 in Spraque-Dawley rats within 6 hours after birth. Rats exposed to air were used as the control group. The lungs from groups aged postnatal days 3, 7 and 14 were removed and dissected from the main bronchi for analysis. Eight rats of each group were used to assess expression of FABP4 in lungs by immunohistochemistry and ELISA. Lung FABP4 mRNA levels were measured by semi-quantitative reverse transcription polymerase chain reaction. The levels of FABP4 in BALF were measured using ELISA. Results FABP4 immunoreactivity was detected in the majority of alveolar macrophages, bronchial epithelial cells and endothelial cells. FABP4 protein levels in lung tissues in the hyperoxic exposure group increased signiifcantly compared with the control group on days 3, 7 and 14 after birth （P〈0.05）, and FABP4 mRNA levels in lung tissues also increased signiifcantly in the hyperoxic exposure group compared with the control group on days 7 and 14 after birth （P〈0.05）. The hyperoxic exposure group demonstrated increased FABP4 levels in BALF compared with the control group on days 7 and 14 after birth （P〈0.05）. Conclusions FABP4 levels increase in preterm rat lungs after hyperoxic lung injury, which may contribute to the pathogenesis of BPD.