Hyperoxia−hypoxia exposure is a proposed cause of alveolar developmental arrest in bronchopulmonary dysplasia in preterm infants, where mitochondrial reactive oxygen species and oxidative stress vulnerability are increased. The aryl hydrocarbon receptor (AhR) is one of the main activators of the antioxidant enzyme system that protects tissues and systems from damage. The present study aimed to determine if the activation of the AhR signaling pathway by prenatal administration of indole-3-carbinol (I3C) protects rat pups from hyperoxia–hypoxia-induced lung injury. To assess the activation of protein-encoding genes related to the AhR signaling pathway (Cyp1a1, Cyp1b1, Ugt1a6, Nqo1, and Gsta1), pup lungs were excised at 0, 24, and 72 h after birth, and mRNA expression levels were quantified by reverse transcription-quantitative polymerase chain reaction assays (RT-qPCR). An adapted Ratner's method was used in rats to evaluate radial alveolar counts (RACs) and the degree of fibrosis. The results reveal that the relative expression of AhR-related genes in rat pups of prenatally I3C-treated dams was significantly different from that of untreated dams. The RAC was significantly lower in the hyperoxia–hypoxia group (4.0 ± 1.0) than that in the unexposed control group (8.0 ± 2.0; P < 0.01). When rat pups of prenatally I3C-treated dams were exposed to hyperoxia–hypoxia, an RAC recovery was observed, and the fibrosis index was similar to that of the unexposed control group. A cytokine antibody array revealed an increase in the NF-κB signaling cascade in I3C-treated pups, suggesting that the pathway could regulate the inflammatory process under the stimulus of this compound. In conclusion, the present study demonstrates that I3C prenatal treatment activates AhR-responsive genes in pup’s lungs and hence attenuates lung damage caused by hyperoxia–hypoxia exposure in newborns.

高氧 - 低氧暴露是早产儿支气管肺发育不良肺泡发育停滞的一个原因，其中线粒体活性氧和氧化应激脆弱性增加。芳烃受体 (AhR) 是保护组织和系统免受损伤的抗氧化酶系统的主要激活剂之一。本研究旨在确定通过产前给予吲哚-3-甲醇 (I3C) 激活 AhR 信号通路是否可以保护幼鼠免受高氧-缺氧诱导的肺损伤。评估与 AhR 信号通路相关的蛋白质编码基因（Cyp1a1、Cyp1b1、Ugt1a6、Nqo1和Gsta1 ）的激活)，在出生后 0、24 和 72 小时切除幼犬肺，并通过逆转录定量聚合酶链反应测定 (RT-qPCR) 定量 mRNA 表达水平。在大鼠中使用了一种适应的 Ratner 方法来评估径向肺泡计数 (RAC) 和纤维化程度。结果表明，AhR相关基因在产前I3C处理母鼠的幼鼠中的相对表达与未处理母鼠的显着不同。高氧缺氧组的 RAC 显着低于未暴露对照组（4.0 ± 1.0）（8.0 ± 2.0；P  < 0.01)。当产前 I3C 处理的母鼠的幼鼠暴露于高氧 - 低氧时，观察到 RAC 恢复，并且纤维化指数与未暴露的对照组相似。细胞因子抗体阵列显示 I3C 处理的幼崽中 NF-κB 信号级联增加，表明该途径可以在这种化合物的刺激下调节炎症过程。总之，本研究表明，I3C 产前治疗可激活幼犬肺部的 AhR 反应基因，从而减轻新生儿因高氧-低氧暴露引起的肺损伤。