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血管内和细胞外测量是否能始终如一地反映细胞内 pO?

Do Vascular and Extracellular Measurements Consistently Reflect Intracellular pO?

机构信息

Department of Chemistry, New Mexico Institute of Mining and Technology, Socorro, NM, USA.

出版信息

Adv Exp Med Biol. 2023;1438:185-190. doi: 10.1007/978-3-031-42003-0_29.

DOI:10.1007/978-3-031-42003-0_29
PMID:37845459
Abstract

Oxygen measurements are routinely made either in the vasculature or in the extracellular fluid surrounding the cells of tissues. Yet, metabolic oxygen availability depends on the pO within the cells, as does the enhancing effect of oxygen on radiotherapy outcomes. This article reports quantitative modeling work examining the effect of cellular plasma membrane composition on tissue permeability, as a window into tissue oxygen gradients. Previous application of the model indicates that lipid-mediated diffusion pathways accelerate oxygen transfer from capillaries to intracellular compartments and that the extent of acceleration is modulated by membrane lipid and protein composition. Here, the effects of broken intercellular junctions and increased gap size between cells in the model are addressed. The conclusion is reached that the pO gradient will likely be consistent among similar, healthy tissues but may increase with increased interstitial fluid fraction and broken intercellular junctions. Therefore, tissue structural changes in tumors and other diseased or damaged tissues may lead to aberrations in permeability that confound interpretation of extracellular oxygen measurements.

摘要

氧测量通常在脉管系统或细胞周围的细胞外液中进行。然而,代谢氧的可用性取决于细胞内的 pO,氧对放射治疗结果的增强作用也是如此。本文报告了定量建模工作,研究了细胞膜组成对组织通透性的影响,作为组织氧梯度的一个窗口。该模型的先前应用表明,脂质介导的扩散途径可加速氧从毛细血管向细胞内隔室的转移,而加速的程度受膜脂质和蛋白质组成的调节。在这里,模型中细胞间连接的中断和细胞间间隙增大的影响得到了研究。结论是,类似的健康组织中 pO 梯度可能是一致的,但随着细胞外液分数和细胞间连接中断的增加,pO 梯度可能会增加。因此,肿瘤和其他疾病或受损组织中的组织结构变化可能导致渗透性异常,从而混淆对细胞外氧测量的解释。

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本文引用的文献

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Updated Evaluation of Cholesterol's Influence on Membrane Oxygen Permeability.胆固醇对膜氧通透性影响的最新评估。
Adv Exp Med Biol. 2021;1269:23-30. doi: 10.1007/978-3-030-48238-1_4.
2
Simulation Study of Breast Cancer Lipid Changes Affecting Membrane Oxygen Permeability: Effects of Chain Length and Cholesterol.乳腺癌脂质变化对膜氧渗透性影响的模拟研究:链长和胆固醇的影响。
Adv Exp Med Biol. 2021;1269:15-21. doi: 10.1007/978-3-030-48238-1_3.
3
How does oxygen diffuse from capillaries to tissue mitochondria? Barriers and pathways.
氧气如何从毛细血管扩散到组织线粒体?障碍和途径。
J Physiol. 2021 Mar;599(6):1769-1782. doi: 10.1113/JP278815. Epub 2020 Dec 18.
4
Biological validation of electron paramagnetic resonance (EPR) image oxygen thresholds in tissue.组织中电子顺磁共振(EPR)图像氧阈值的生物学验证。
J Physiol. 2021 Mar;599(6):1759-1767. doi: 10.1113/JP278816. Epub 2020 Jun 28.
5
Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression.乳腺癌进展中改变的膜脂代谢特征带来的新型治疗策略。
Cancer Res. 2011 May 1;71(9):3236-45. doi: 10.1158/0008-5472.CAN-10-3894. Epub 2011 Mar 17.