Song Dan, Wang Mengjie, Zhao Xinjie, Zhang Yanru, Zhang Yiyi, Hao Xiaohua, Yuan Jialu, Tang Haojie
Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang 712082, China.
Int J Mol Sci. 2025 Jan 2;26(1):341. doi: 10.3390/ijms26010341.
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.
青藏高原，素有“世界屋脊”之称，前往该地旅行或工作的人数激增。然而，这些人中相当一部分可能会患上急性高原病（AMS），其中高原肺水肿（HAPE）是一种严重且可能危及生命的表现形式。HAPE会破坏肺内组织液的平衡，导致严重的肺功能损害。目前针对HAPE的治疗干预存在局限性，且伴有明显的副作用。醛糖还原酶（AR）是多元醇代谢途径中的一种关键酶，与多种疾病有关。在本研究中，我们试图探究AR在HAPE中的作用。利用体内和体外模型，我们研究了AR对缺氧诱导的肺水肿、血管压力、炎症因子和氧化应激的影响。我们的研究结果表明，敲低AR可减轻缺氧诱导的肺水肿，降低血管压力和炎症因子的表达，并增强与氧化应激相关的表达。这些结果表明，AR可能是HAPE的一个潜在治疗靶点，为预防和治疗这种疾病提供了合理的病理基础和新的药物靶点。
