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从实验到模拟:红细胞对不同氧饱和度水平的剪切诱导反应

From Experiments to Simulation: Shear-Induced Responses of Red Blood Cells to Different Oxygen Saturation Levels.

作者信息

Ugurel Elif, Piskin Senol, Aksu Ali Cenk, Eser Aysenur, Yalcin Ozlem

机构信息

Department of Physiology, School of Medicine, Koç University, Istanbul, Turkey.

Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, Turkey.

出版信息

Front Physiol. 2020 Jan 22;10:1559. doi: 10.3389/fphys.2019.01559. eCollection 2019.

DOI:10.3389/fphys.2019.01559
PMID:32038272
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6987081/
Abstract

Red blood cells (RBC) carry and deliver oxygen (O) to peripheral tissues through different microcirculatory regions where they are exposed to various levels of shear stress (SS). O affinity of hemoglobin (Hb) decreases as the blood enters the microcirculation. This phenomenon determines Hb interactions with RBC membrane proteins that can further regulate the structure of cytoskeleton and affect the mechanical properties of cells. The goal of this study is to evaluate shear-induced RBC deformability and simulate RBC dynamics in blood flow under oxygenated and deoxygenated conditions. Venous blood samples from healthy donors were oxygenated with ambient air or deoxygenated with 100% nitrogen gas for 10 min and immediately applied into an ektacytometer (LORRCA). RBC deformability was measured before and after the application of continuous 5 Pa SS for 300 s by LORRCA and recorded as elongation index (EI) values. A computational model was generated for the simulation of blood flow in a real carotid artery section. EI distribution throughout the artery and its relationships with velocity, pressure, wall SS and viscosity were determined by computational tools. RBC deformability significantly increased in deoxygenation compared to oxygenated state both before and after 5 Pa SS implementation ( < 0.0001). However, EI values after continuous SS were not significant at higher SS levels (>5.15 Pa) in deoxygenated condition. Simulation results revealed that the velocity gradient dominates the generation of SS and the shear thinning effect of blood has a minor effect on it. Distribution of EI was calculated during oxygenation/deoxygenation which is 5-10 times higher around the vessel wall compared to the center of the lumen for sections of the pulsatile flow profile. The extent of RBC deformability increases as RBCs approach to the vessel wall in a real 3D artery model and this increment is higher for deoxygenated condition compared to the oxygenated state. Hypoxia significantly increases shear-induced RBC deformability. RBCs could regulate their own mechanical properties in blood flow by increasing their deformability in hypoxic conditions. Computational tools can be applied for defining hypoxia-mediated RBC deformability changes to monitor blood flow in hypoxic tissues.

摘要

红细胞(RBC)通过不同的微循环区域携带并将氧气(O)输送到外周组织,在这些区域它们会受到不同水平的剪切应力(SS)。随着血液进入微循环,血红蛋白(Hb)的氧亲和力降低。这种现象决定了Hb与RBC膜蛋白的相互作用,这可以进一步调节细胞骨架的结构并影响细胞的力学性能。本研究的目的是评估剪切诱导的RBC变形能力,并模拟在充氧和脱氧条件下血流中的RBC动力学。从健康供体采集的静脉血样本用环境空气充氧或用100%氮气脱氧10分钟,然后立即应用于红细胞变形仪(LORRCA)。在通过LORRCA施加连续5 Pa的SS 300秒之前和之后测量RBC变形能力,并记录为伸长指数(EI)值。生成了一个计算模型来模拟真实颈动脉段中的血流。通过计算工具确定整个动脉中的EI分布及其与速度、压力、壁面SS和粘度的关系。在实施5 Pa SS之前和之后,与充氧状态相比,脱氧状态下的RBC变形能力显著增加(<0.0001)。然而,在脱氧条件下,在较高的SS水平(>5.15 Pa)下,连续SS后的EI值不显著。模拟结果表明,速度梯度主导了SS的产生,血液的剪切变稀效应对此影响较小。计算了在充氧/脱氧过程中的EI分布,对于脉动流剖面的各部分,与管腔中心相比,在血管壁周围高5-10倍。在真实的三维动脉模型中,随着RBC接近血管壁,RBC变形能力的程度增加,并且与充氧状态相比,脱氧条件下的这种增加更高。缺氧显著增加剪切诱导的RBC变形能力。RBC可以通过在缺氧条件下增加其变形能力来调节其在血流中的自身力学性能。计算工具可用于定义缺氧介导的RBC变形能力变化,以监测缺氧组织中的血流。

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