高原低氧环境对肿瘤发生发展的影响及其分子机制研究进展

Advances in the study of the impact of the hypoxic plateau environment on tumor initiation, progression, and molecular mechanisms

摘要:

高原低氧环境对人体生理功能具有广泛影响，尤其对肿瘤发生发展的作用近年来备受关注。本文重点综述了高原低氧环境通过缺氧诱导因子 （HIF） 信号通路、氧化应激反应及免疫微环境改变等分子机制对肿瘤生物学行为的影响。研究表明，持续低氧环境可稳定 HIF-1α表达，进而调控下游靶基因，影响肿瘤血管生成、能量代谢重编程和细胞凋亡抵抗。 同时，高原强紫外线与低氧协同作用可增加活性氧生成，导致DNA损伤及基因组不稳定性。此外，高原低氧环境还能诱导髓源性抑制细胞浸润增加和PD-L1表达上调，促进肿瘤免疫逃逸。本文还总结了针对高原低氧环境的肿瘤预防策略，包括 HIF信号通路靶向干预、抗氧化治疗和免疫调节等，以期为高原地区肿瘤防治提供科学依据。

Abstract:

The hypoxic plateau environment has a broad impact on human physiological function, and its role in tumor initiation and progression has attracted increasing attention in recent years. This review focuses on the effects of the hypoxic plateau environment on tumor biological behavior through the hypoxia-inducible factor (HIF) signaling pathway, oxidative stress response, and changes in the immune microenvironment. Studies have shown that continuous hypoxia can stabilize the expression of HIF-1α, thereby regulating downstream target genes and affecting tumor angiogenesis, energy metabolic reprogramming, and resistance to apoptosis. At the same time, the synergistic effect of strong ultraviolet radiation and hypoxia in the plateau environment can increase the production of reactive oxygen species (ROS), leading to DNA damage and genomic instability. In addition, the hypoxic plateau environment can induce increased myeloid-derived suppressor cell (MDSC) infiltration and upregulation of PD-L1 expression, promoting tumor immune escape. This paper also summarizes tumor prevention strategies for the hypoxic plateau environment, including targeted interventions in the HIF pathway, antioxidant therapy, and immunomodulation, aiming to provide a scientific basis for tumor prevention and treatment in plateau regions.