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在微流体多孔状网络中他汀类药物处理的红细胞动力学。

Statin-treated RBC dynamics in a microfluidic porous-like network.

作者信息

Stathoulopoulos Antonios, König Carola S, Ramachandran Sudarshan, Balabani Stavroula

机构信息

FluME, Department of Mechanical Engineering, University College London, London, UK.

Department of Mechanical and Aerospace Engineering, Brunel University of London, Uxbridge, UK.

出版信息

Microvasc Res. 2025 Mar;158:104765. doi: 10.1016/j.mvr.2024.104765. Epub 2024 Nov 19.

DOI:10.1016/j.mvr.2024.104765
PMID:39571747
Abstract

The impact of therapeutic interventions on red blood cell (RBC) deformability and microscale transport is investigated, using statins as an exemplar. Human RBCs were treated in vitro with two commonly prescribed statins, atorvastatin and rosuvastatin, at clinically relevant concentrations. Changes in RBC deformability were quantified using a microfluidic-based ektacytometer and expressed in terms of the elongation index. Dilute suspensions of the statin-treated RBCs were then perfused through a microfluidic pillar array, at a constant flow rate and negligible inertia, and imaged. Particle Tracking Velocimetry (PTV) was applied to track RBCs, identify preferential paths and estimate their velocities, whereas image processing was used to estimate cell dynamics, perfusion metrics and distributions. The findings were compared against those of healthy, untreated cells. Statins enhanced RBC deformability in agreement with literature. The extent of enhancement was found to be statin-dependent. The softer statin-treated cells were found to flow in straight, less tortuous paths, spend more time inside the pillar array and exhibit lower velocities compared to healthy RBCs, attributed to their enhanced deformation and longer shape recovery time upon impact with the array posts. The in vitro microfluidic approach demonstrated here may serve as a monitoring tool to personalise and maximise the outcome of a therapeutic treatment.

摘要

以他汀类药物为例,研究了治疗干预对红细胞(RBC)变形性和微观尺度运输的影响。使用两种常用的处方他汀类药物阿托伐他汀和瑞舒伐他汀,在临床相关浓度下对人红细胞进行体外处理。使用基于微流控的血细胞变形仪对红细胞变形性的变化进行定量,并以伸长指数表示。然后,以恒定流速和可忽略的惯性,将经他汀类药物处理的红细胞的稀释悬浮液灌注通过微流控柱阵列,并进行成像。应用粒子跟踪测速技术(PTV)跟踪红细胞,识别优先路径并估计其速度,而图像处理则用于估计细胞动力学、灌注指标和分布。将研究结果与健康的未处理细胞进行比较。他汀类药物增强了红细胞变形性,这与文献一致。发现增强程度取决于他汀类药物。与健康红细胞相比,经他汀类药物处理后较软的细胞以更直、更不曲折的路径流动,在柱阵列内停留的时间更长,并且速度更低,这归因于它们在与阵列柱碰撞时增强的变形和更长的形状恢复时间。本文展示的体外微流控方法可作为一种监测工具,用于个性化治疗并最大化治疗效果。

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