Controlled Ascent Rate Enhances Autophagy and Mitigates Acute Lung Injury in Rats Exposed to High‐Altitude Hypoxia by Inhibiting Oxidative Stress and Inflammation

The gradual ascent strategy, an effective measure to prevent acute mountain sickness by enabling the body to adapt to high-altitude hypoxia, has an unclear mechanism. This study explores controlled ascent rates' effects on autophagy, oxidative stress, inflammation, and lung injury in rats exposed to high-altitude hypoxia, hypothesizing that gradual ascent can activate autophagy, reduce oxidative stress and inflammation, and improve lung injury. 70 male Sprague-Dawley rats are divided into seven groups, including a normal control group and high-altitude hypoxia for 24, 72, and 120 h, with or without controlled ascent rates. Lung tissues are analyzed for the wet-to-dry weight ratio, histopathology, inflammatory cytokines, oxidative stress markers, and autophagy-related protein expression. Results show that controlled ascent rates reduced lung injury, oxidative stress, and inflammation in rats exposed to high-altitude hypoxia while increasing autophagy. This study indicates that gradual ascent can be an effective strategy for reducing lung injury in high-altitude areas by regulating autophagy and reducing oxidative stress and inflammation.