In the NICU, bronchopulmonary dysplasia (BPD) is a concerning common respiratory complication in preterm and low birth-weight infants. Clinical studies have confirmed that human milk has an important nutritional role for children with BPD, therefore, dentification of beneficial components in human milk that prevent BPD is urgently needed. Our previous work showed that human milk exosomes (HM-Exos) could inhibit apoptosis of alveolar type II epithelial cells (AT II), and the circular RNA (circRNA)-circABPD1 were highly expressed in preterm colostrum milk exosomes. Exosomes transport circRNAs that are stable and may exert anti-inflammatory and immune effects attracted the attention of researchers, but the role and mechanism of human milk exosome-derived circABPD1 in BPD remains unclear. Here, we constructed BPD in vivo and in vitro models through exposure to hyperoxia, verified the effect of circABPD1 and revealed its mechanism through rescue experiments. We found that circABPD1 had circRNA properties, and overexpression of circABPD1 could improve reduced alveolar number, enlarged the alveolar linear intercept in vivo models of BPD, promote cell proliferation, reduce oxidative stress levels and alleviate lung epithelial cell damage in vivo and in vitro models. Mechanistically, circABPD1 targets miR-330–3p and regulates the expression of HIF1α. These results suggest that circABPD1 can improve the pathologoical changes of bronchopulmonary dysplasia, promote cell proliferation, inhibit oxidative stress level, and alleviate lung injury by targeting the miR-330–3p/HIF1α axis, which provides a new idea for the prevention and treatment of bronchopulmonary dysplasia.

在 NICU 中，支气管肺发育不良 (BPD) 是早产儿和低出生体重儿常见的呼吸系统并发症。临床研究证实，母乳对 BPD 儿童具有重要的营养作用，因此，迫切需要鉴定母乳中预防 BPD 的有益成分。我们前期的工作表明，母乳外泌体（HM-Exos）可以抑制肺泡II型上皮细胞（AT II）的凋亡，并且环状RNA（circRNA）-circABPD1在早产初乳外泌体中高表达。外泌体运输稳定且可能发挥抗炎和免疫作用的circRNA引起了研究人员的关注，但母乳外泌体来源的circABPD1在BPD中的作用和机制仍不清楚。在这里，我们通过高氧暴露构建了BPD体内和体外模型，验证了circABPD1的作用并通过救援实验揭示了其机制。我们发现circABPD1具有circRNA特性，并且circABPD1的过度表达可以改善BPD体内模型中减少的肺泡数量，扩大肺泡线性截距，促进细胞增殖，降低氧化应激水平并减轻体内和体外模型中的肺上皮细胞损伤。从机制上讲，circABPD1 靶向 miR-330–3p 并调节 HIF1α 的表达。这些结果提示，circABPD1可通过靶向miR-330–3p/HIF1α轴，改善支气管肺发育不良的病理改变，促进细胞增殖，抑制氧化应激水平，减轻肺损伤，为支气管肺发育不良的防治提供新思路。支气管肺发育不良。