MSC‐EXO and tempol ameliorate bronchopulmonary dysplasia in newborn rats by activating HIF‐1α

作者：Juanmei Wang, Aimin Zhang, Furong Huang, Jun Xu, Menghua Zhao · 发表于：Pediatric Pulmonology · 年份：2023 · DOI：10.1002/ppul.26317 · 被引用次数：15 · 研究领域：Neonatal Respiratory Health Research、Extracellular vesicles in disease、Mesenchymal stem cell research

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major complication of premature infants and an important cause of morbidity and mortality. This study investigates the effect of the combination of mesenchymal stem cells-derived exosomes (MSC-EXO) and tempol on BPD and analyzes its mechanism. METHODS: MSC-EXO was extracted by centrifugation and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis, and western blot analysis (WB). Tidal volume (TV), minute ventilation (MV), peak inspiratory flow (PIF), and dynamic pulmonary compliance (Cdyn) of rats were measured by BuxCo pulmonary function experimental platform. Hematoxylin-eosin staining was performed to observe the lung morphology and radical alveolar count (RAC) and mean linear intercept (MLI) were assessed. Immunofluorescence (IF) was conducted to detect the expression of CD31 and α-SMA in pulmonary blood vessels. The kits were used to calculate malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (TAOC) concentration in lung tissue. Enzyme linked immunosorbent assay was applied to detect the levels of IL-1β, IL-17, IL-6, and IFN-γ in bronchoalveolar lavage fluid. In addition, the expressions of HIF-1α, vascular endothelial growth factor (VEGF), p-PI3K, and p-AKT were analyzed by WB and IF. RESULTS: We successfully extracted and identified MSC-EXO. In BPD rats, TV, MV, PIF, and Cdyn decreased, alveoli were simplified, and the number of interalveoli small vessels,...