Abstract

High-altitude pulmonary edema (HAPE) is a life-threatening disorder caused by hypobaric hypoxia and characterized by pulmonary injury, oxidative stress, and inflammation. We investigated the effects of small extracellular vesicles derived from dental pulp stem cells (DPSCs-sEVs) in a rat model of HAPE as well as hypoxia-injured pulmonary microvascular endothelial cells (PMVECs). Rats were exposed to hypobaric hypoxia for 96 h. Lung injury was assessed by histology and immunofluorescence (VEGF, TNF-α, Occludin). Pulmonary permeability was evaluated by total protein in bronchoalveolar lavage fluid and lung homogenates and by Na + /K + -ATPase activity. Oxidative stress, inflammatory mediators, and vasoactive factors (NO, PGI₂) were measured. DPSCs-sEVs attenuated hypoxia-induced lung injury, increased VEGF and Occludin, reduced TNF-α, decreased protein leakage, and enhanced Na + /K + -ATPase activity. DPSCs-sEVs alleviated oxidative stress and upregulated Nrf2, HO-1, and GPX1. In vivo, dexamethasone served as a reference treatment; DPSCs-sEVs produced greater improvements in most endpoints, with comparable effects in selected measures. In PMVECs, DPSCs-sEVs dose-dependently mitigated hypoxia-induced dysfunction. These findings suggest DPSCs-sEVs protect against hypoxia-induced pulmonary injury by preserving barrier integrity and improving redox and inflammatory homeostasis.