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 afterhyperoxic lung injury

摘要:

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.

Abstract:

Objective To study the expression of fatty acid binding protein 4 (FABP4) in lungs and bron choalveolar lavage fluid (BALF) of preterm rats exposed to 60% O₂ and to elucidate the relationship between thechanges of FABP4 expression and the pathogenesis of bronchopulmonary dysplasia (BPD). Methods Hyperoxiclung injury was induced by exposing to 60% O₂ in Spraque-Dawley rats within 6 hours after birth. Rats exposedto 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 inlungs by immunohistochemistry and ELISA. Lung FABP4 mRNA levels were measured by semi-quantitative reversetranscription 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 significantly compared with the controlgroup on days 3, 7 and 14 after birth (P<0.05), and FABP4 mRNA levels in lung tissues also increased significantly inthe hyperoxic exposure group compared with the control group on days 7 and 14 after birth (P<0.05). The hyperoxicexposure group demonstrated increased FABP4 levels in BALF compared with the control group on days 7 and 14after birth (P<0.05). Conclusions FABP4 levels increase in preterm rat lungs after hyperoxic lung injury, which maycontribute to the pathogenesis of BPD.