Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
J Cell Mol Med. 2020 Jan;24(1):965-972. doi: 10.1111/jcmm.14808. Epub 2019 Nov 12.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects the quality of life of infants. At present, premature exposure to hyperoxia for extended periods of time is believed to affect the development of lung tissue and vascularity, resulting in BPD. The oxidative stress caused by hyperoxia exposure is an important risk factor for BPD in premature infants. Nuclear factor E2-related factor 2 (Nrf2) is an important regulator of antioxidant mechanisms. As a microRNA, microRNA-125b (miR-125b) plays an important role in cell proliferation, differentiation and apoptosis. Although the Nrf2/ARE pathway has been extensively studied, little is known about the regulatory role of microRNAs in Nrf2 expression. In this study, the expression levels of Nrf2 and miR-125b in the lung tissues of premature Sprague Dawley (SD) rats and A549 cells exposed to hyperoxia were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the apoptosis of A549 cells was detected by flow cytometry. The results showed that Nrf2 and miRNA-125b in the lung tissues of premature rats increased significantly upon exposure to hyperoxia and played a protective role. Nrf2 was suppressed by small interfering RNA (siRNA) in A549 cells, miR-125b was similarly inhibited, and apoptosis was significantly increased. These results suggest that miR-125b helps protect against BPD as a downstream target of Nrf2.
支气管肺发育不良（BPD）是一种影响婴儿生活质量的慢性肺部疾病。目前，早产儿长时间暴露于高氧环境被认为会影响肺组织和血管的发育，从而导致 BPD。高氧暴露引起的氧化应激是早产儿 BPD 的一个重要危险因素。核因子 E2 相关因子 2（Nrf2）是抗氧化机制的重要调节因子。作为一种 microRNA，microRNA-125b（miR-125b）在细胞增殖、分化和凋亡中发挥着重要作用。尽管 Nrf2/ARE 通路已被广泛研究，但对于 microRNAs 在 Nrf2 表达中的调节作用知之甚少。在这项研究中，通过实时定量聚合酶链反应（qRT-PCR）检测了高氧暴露的早产 Sprague Dawley（SD）大鼠和 A549 细胞肺组织中 Nrf2 和 miR-125b 的表达水平，并通过流式细胞术检测了 A549 细胞的凋亡。结果表明，高氧暴露后早产大鼠肺组织中的 Nrf2 和 miRNA-125b 显著增加，发挥保护作用。A549 细胞中的 Nrf2 被小干扰 RNA（siRNA）抑制，miR-125b 也受到类似抑制，细胞凋亡明显增加。这些结果表明，miR-125b 作为 Nrf2 的下游靶点有助于预防 BPD。
