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.
Background Pulmonary hypertension (PH) is a common complication of bronchopulmonary dysplasia (BPD) in very-low-birth-weight infants (VLBWIs). Although recent studies have increased awareness that PH contributes significantly to the high morbidity and mortality of BPD, the risk factors and clinical characteristics for PH in VLBWIs are little known. Objectives To investigate the risk factors and clinical characteristics for BPD-associated pulmonary hypertension (BPD-PH) in VLBWIs. Methods A retrospective case–control observational study of VLBWIs with BPD admitted to a neonatal intensive care unit (NICU) over 4 years. According to echocardiograms confirming elevated pulmonary artery pressure after 28 days after birth, we divided BPD infants into PH group (n = 18) and non-PH group (n = 65). We compared pre- and postnatal characteristics between VLBWIs with or without PH. Multivariable logistic regression analysis was conducted with backward selection. Results A total of 83 infants with BPD were divided into PH group (n = 18) or non-PH group (n = 65). The average birth weight of the infants with BPD was 1078.1 g. Compared with those infants of the non-PH group, the birth weight of BPD-PH infants was significantly lower (968.1 ± 187.7 vs. 1108.5 ± 185.8, P = 0.006). Infants in the PH group had a higher incidence of patent ductus arteriosus (PDA) and underwent longer durations of oxygen therapy and mechanical ventilation compared to those in the non-PH group. In all subjects, birth weight (OR 0.995; 95% CI 0.991–0.999; P = 0.025) and PDA (OR 13.355; 95% CI 2.950–60.469; P = 0.001) were found to be specific risk factors for BPD-PH in this cohort. Conclusions The study shows PDA and birth weight are specific risk factors for BPD-PH in VLBWIs.
Bronchopulmonary dysplasia (BPD) is one of the main causes of chronic lung disease in premature infants. Acute lung injury following exposure to hyperoxia contributes to the development of BPD in preterm infants. The nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway is an endogenous antioxidant defense mechanism that is involved in the pathogenesis of numerous hyperoxia-induced diseases.In the present study, the expression of Nrf2, Kelch-like ECH-associated protein 1 (Keap1) and NAD(P)H quinone oxidoreductase 1 enzyme (NQO1) was detected in A549 cells exposed to hyperoxia and transfection with small interfering RNA (siRNA) using reverse transcription-quantitative polymerase chain reaction and western blotting, and cellular apoptosis was detected using flow cytometry. The results demonstrated that apoptosis increased significantly following exposure of the cells to hyperoxia, and Nrf2, Keap1 and NQO1 expression levels were significantly upregulated under hyperoxic conditions. Furthermore, following transfection with Nrf2 siRNA, the expression levels of these genes were significantly downregulated and apoptosis was significantly increased compared with the respective values in untransfected cells. These findings suggest that the Nrf2-Keap1-antioxidant response element-NQO1 signaling pathway may play a protective role in hyperoxia-induced lung injury via the inhibition of apoptosis.
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