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高海拔低氧暴露持续时间对大鼠脑区氧化稳态的影响。

Impact of Exposure Duration to High-Altitude Hypoxia on Oxidative Homeostasis in Rat Brain Regions.

作者信息

Lira-Mejía Boris, Calderon-Romero Roger, Ordaya-Fierro Jorge, Medina Cristian, Rodríguez José-Luis, Romero Alejandro, Dávila Roberto, Ramos-Gonzalez Mariella

机构信息

GIFATA Research Group, Animal Physiology Laboratory, Faculty of Veterinary Medicine, Major National University of San Marcos, Lima 15021, Peru.

Complutox Research Group, Department of Pharmacology and Toxicology, Faculty of Veterinary, Complutense University of Madrid, 28040 Madrid, Spain.

出版信息

Int J Mol Sci. 2025 Sep 7;26(17):8714. doi: 10.3390/ijms26178714.

Abstract

Hypoxia at altitudes above 3000 m poses a significant threat to organ health and physiological homeostasis, particularly in metabolically active tissues such as the brain. Many of the cellular alterations induced by hypoxia are associated with the excessive generation of reactive oxygen species (ROS) and the resulting oxidative stress. In this study, we investigated the effects of exposure duration and altitude levels on oxidative homeostasis in the rat hypothalamus, cortex, hippocampus, and striatum. We assessed ROS production, malondialdehyde (MDA) levels, the antioxidant activities of superoxide dismutase (SOD), and catalase, as well as molecular biomarkers of oxidative stress, cell death, and inflammation. Our findings demonstrated that ROS, MDA and SOD levels increased across all brain regions, particularly in response to higher altitude exposure. Conversely, catalase activity decreased under the same conditions. At the molecular level, we observed overexpression of key biomarkers related to oxidative stress, cell death, and inflammation, especially at extreme altitudes. Furthermore, these effects were most pronounced in the hippocampus, cortex, and striatum. In conclusion, our data indicate that hypoxic exposure at higher altitudes significantly contributes to the oxidative disruption of brain homeostasis in rats.

摘要

海拔3000米以上的低氧环境对器官健康和生理稳态构成重大威胁,尤其是对大脑等代谢活跃的组织。低氧诱导的许多细胞改变与活性氧(ROS)的过度产生及由此产生的氧化应激有关。在本研究中,我们调查了暴露持续时间和海拔高度对大鼠下丘脑、皮层、海马体和纹状体氧化稳态的影响。我们评估了ROS的产生、丙二醛(MDA)水平、超氧化物歧化酶(SOD)和过氧化氢酶的抗氧化活性,以及氧化应激、细胞死亡和炎症的分子生物标志物。我们的研究结果表明,所有脑区的ROS、MDA和SOD水平均升高,尤其是在暴露于更高海拔时。相反,在相同条件下过氧化氢酶活性降低。在分子水平上,我们观察到与氧化应激、细胞死亡和炎症相关的关键生物标志物的过表达,尤其是在极端海拔高度。此外,这些影响在海马体、皮层和纹状体中最为明显。总之,我们的数据表明,高海拔低氧暴露显著导致大鼠脑内稳态的氧化破坏。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a44d/12429807/d581c450fd63/ijms-26-08714-g001.jpg

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