肿瘤缺氧是一种动态现象，其特征是氧气水平在快速（秒到分钟）和慢速（小时到天）时间尺度上波动。虽然短缺氧周期相对较好，但较长周期背后的机制仍不清楚。在本文中，我们提出了一种新颖的机械数学模型，该模型通过涉及血管扩张和消退、氧调节的肿瘤生长和有毒细胞因子产生的反馈回路来解释缓慢的缺氧循环。我们的研究表明，对于缓慢缺氧周期的出现，内皮细胞必须通过随着配体浓度的增加而减少受体激活来适应。此外，肿瘤细胞和毒性细胞因子之间的相互作用影响这些周期的频率和强度。通过检查药物干预措施，特别是聚（ADP-核糖）聚合酶抑制剂的效果，我们还证明了靶向细胞增殖如何帮助调节氧水平。我们的研究结果增强了对缺氧调节的理解，并表明 PARP 蛋白是有希望的治疗靶点。© 2024。作者。

Tumor hypoxia is a dynamic phenomenon marked by fluctuations in oxygen levels across both rapid (seconds to minutes) and slow (hours to days) time scales. While short hypoxia cycles are relatively well understood, the mechanisms behind longer cycles remain largely unclear. In this paper, we present a novel mechanistic mathematical model that explains slow hypoxia cycles through feedback loops involving vascular expansion and regression, oxygen-regulated tumor growth, and toxic cytokine production. Our study reveals that, for the emergence of slow hypoxia cycles, endothelial cells must adapt by decreasing receptor activation as ligand concentration increases. Additionally, the interaction between tumor cells and toxic cytokines influences frequency and intensity of these cycles. By examining the effects of pharmacological interventions, specifically poly (ADP-ribose) polymerase inhibitors, we also demonstrate how targeting cell proliferation can help regulate oxygen levels. Our findings enhance the understanding of hypoxia regulation and suggest PARP proteins as promising therapeutic targets.© 2024. The Author(s).