European journal of pharmacology · 2025
Modulation of HIF1α/CXCR4 by CDDP, acetazolamide, and salidroside in early lung injury caused by acute high-altitude hypoxia.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wang Fei, Zhang Yiman, Liu Bing, Liu Jia, Lai Baochang, Jia Pu, Zhang Junbo, Ma Qiang, Meng Yan, Zhao Ye, Wuren Tana, Zheng Xiaohui, Tian Hongyan, Yin Qian
Аннотация
BACKGROUND: The inflammatory response of pulmonary vascular endothelial cells is critical in the pathogenesis of hypobaric hypoxia-induced acute lung injury. Elucidation of the underlying mechanisms and potential therapeutic interventions is crucial for both medical professionals and individuals exposed to high altitudes.
METHODS: A murine model of acute lung injury was established by subjecting mice to hypobaric hypoxia at an altitude equivalent to 6000 m for 8 and 72 h. Histopathological and immunohistochemical analyses were performed using hematoxylin-eosin staining and immunohistochemistry to assess inflammation. Western blotting for Endothelial Nitric Oxide Synthase (eNOS) phosphorylation was used to evaluate endothelial injury. High-throughput RNA sequencing was employed to identify early inflammatory regulators, and the protein expression of Hypoxia inducible factor-1 (HIF1α), C-X-C chemokine receptor 4 (CXCR4) and Phospho-Endothelial Nitric Oxide Synthase (p-eNOS) was examined via western blotting. Additionally, the expression level of CXCR4 and selected cytokines were quantified by real-time Polymerase Chain Reaction.
RESULTS: Lung tissues demonstrated marked inflammatory infiltration and lung injury after 8 h of hypobaric hypoxia exposure, peaking at 24 h. HIF1α expression was significantly upregulated at 8 h and gradually decreased thereafter. CXCR4, identified as a target gene of HIF1α, exhibited a similar expression pattern. Preventive treatment with compound Danshen dripping pills, acetazolamide and salidroside accelerated the suppression of HIF1α and CXCR4 expression compared to the natural response following 8 h of hypobaric hypoxia. Furthermore, these agents demonstrated enhanced protective effects against endothelial dysfunction and inflammation.
CONCLUSIONS: These findings indicate that the endothelial HIF1α/CXCR4 axis plays a pivotal role in the early phase of hypobaric hypoxia-induced acute lung injury. The downregulation of HIF1α/CXCR4 by compound Danshen dripping pills, acetazolamide and salidroside suggests promising therapeutic strategies for managing acute high-altitude hypoxic lung injury.
METHODS: A murine model of acute lung injury was established by subjecting mice to hypobaric hypoxia at an altitude equivalent to 6000 m for 8 and 72 h. Histopathological and immunohistochemical analyses were performed using hematoxylin-eosin staining and immunohistochemistry to assess inflammation. Western blotting for Endothelial Nitric Oxide Synthase (eNOS) phosphorylation was used to evaluate endothelial injury. High-throughput RNA sequencing was employed to identify early inflammatory regulators, and the protein expression of Hypoxia inducible factor-1 (HIF1α), C-X-C chemokine receptor 4 (CXCR4) and Phospho-Endothelial Nitric Oxide Synthase (p-eNOS) was examined via western blotting. Additionally, the expression level of CXCR4 and selected cytokines were quantified by real-time Polymerase Chain Reaction.
RESULTS: Lung tissues demonstrated marked inflammatory infiltration and lung injury after 8 h of hypobaric hypoxia exposure, peaking at 24 h. HIF1α expression was significantly upregulated at 8 h and gradually decreased thereafter. CXCR4, identified as a target gene of HIF1α, exhibited a similar expression pattern. Preventive treatment with compound Danshen dripping pills, acetazolamide and salidroside accelerated the suppression of HIF1α and CXCR4 expression compared to the natural response following 8 h of hypobaric hypoxia. Furthermore, these agents demonstrated enhanced protective effects against endothelial dysfunction and inflammation.
CONCLUSIONS: These findings indicate that the endothelial HIF1α/CXCR4 axis plays a pivotal role in the early phase of hypobaric hypoxia-induced acute lung injury. The downregulation of HIF1α/CXCR4 by compound Danshen dripping pills, acetazolamide and salidroside suggests promising therapeutic strategies for managing acute high-altitude hypoxic lung injury.