Abstract
The Qinghai-Tibet Plateau, famously known as the "Roof of the World", has witnessed a surge in individuals traveling or working there. However, a considerable percentage of these individuals may suffer from acute mountain sickness (AMS), with high-altitude pulmonary edema (HAPE) being a severe and potentially life-threatening manifestation. HAPE disrupts the balance of intrapulmonary tissue fluid, resulting in severe lung function impairment. Current therapeutic interventions for HAPE have limitations and are accompanied by significant side effects. Aldose reductase (AR), a crucial enzyme in the polyol metabolic pathway, has been implicated in various diseases. In this study, we sought to explore the role of AR in HAPE. Utilizing both in vivo and in vitro models, we investigated the impact of AR on hypoxia-induced pulmonary edema, vascular pressure, inflammatory factors, and oxidative stress. Our findings revealed that AR knockdown mitigated hypoxia-induced pulmonary edema, decreased the expression of vascular pressure and inflammatory factors, and enhanced the expression related to oxidative stress. These results indicate that AR may serve as a potential therapeutic target for HAPE, offering a plausible pathological basis and novel drug targets for the prevention and treatment of this condition.