Effects of different shear rates on the attachment and detachment of platelet thrombi.
Effects of different shear rates on the attachment and detachment of platelet thrombi.
复制标题
不同剪切速率对血小板血栓附着与脱离的影响
DOI：
10.3892/mmr.2016.4825
复制
发表时间：
2016-03
影响因子：
3.4
通讯作者：
Xi X
中科院分区：
文献类型：
--
作者：
Shi X;Yang J;Huang J;Long Z;Ruan Z;Xiao B;Xi X
血栓和止血发生在流动的血液中，产生剪切力。不同的切变率，特别是病理性作用力对血小板血栓形成的影响仍有待充分阐明。本研究观察了在不同壁面剪切率(WSR)下胶原表面血栓的形态特征和分级结构，并探讨了其潜在机制。用Bioflow 200型微流控装置以设定的不同剪切速率将钙黄素AM标记的全血灌流到胶原蛋白涂层表面，评估形成的血栓的面积覆盖率、高度和由血小板激活程度和填充密度定义的分级结构。并对影响血栓形成的因素进行了探讨。不同WSR下形成的血小板血栓不同，如S−1125~250时可见分散的血小板与红细胞粘连，S−1时可见广泛而细小的血小板血栓，2,500~5,000 S−1时可见散在的粗大血栓，呈脱落趋势。随着WSR的增加，血栓高度呈线性增加，而血栓的总荧光强度和面积呈抛物线型变化，在WSR为2,500 S−1时有一个转折点。血栓数目、平均荧光强度和每血栓面积也呈现类似的趋势，先上升后下降。在WSR较高时形成的血栓具有较厚的外壳，这导致核心更加紧密地堆积。剪切流条件下血小板血栓的形成受受体-配体相互作用、剪切率诱导的血小板沉积和流动动态力引起的脱壁等因素的调节。这导致了血栓附着(包括粘连和聚集)和脱离之间的平衡。总体而言，与生理性低WSR相比，病理性高WSR会导致血栓更厚、更容易脱落，核心凝结更多，这受附着-脱离平衡的调节。这些结果提供了对不同WSR处胶原上血栓形成特性的新见解，并为某些临床生理病理现象提供了可能的解释，包括物理止血和病理性血栓形成。
Thrombosis and hemostasis take place in flowing blood, which generates shear forces. The effect of different shear rates, particularly pathological forces, on platelet thrombus formation remains to be fully elucidated. The present study observed the morphological characteristics and hierarchical structure of thrombi on the collagen surface at a wide range of wall shear rates (WSRs) and examined the underlying mechanisms. Calcein AM-labeled whole blood was perfused over a collagen-coated surface at different shear rates set by a Bioflux 200 microfluidic device and the thrombi formed were assessed for area coverage, the height and the hierarchical structure defined by the extent of platelet activation and packing density. The factors that affect thrombus formation were also investigated. Platelet thrombus formation varied under different WSRs, for example, dispersed platelet adhesion mixed with erythrocytes was observed at 125–250 s−1, extensive and thin platelet thrombi were observed at 500–1,500 s−1, and sporadic, thick thrombi were observed at pathological WSRs of 2,500–5,000 s−1, which showed a tendency to be shed. With increasing WSRs, the height of the thrombi showed an increasing linear trend, whereas the total fluorescence intensity and area of the thrombi exhibited a parabolic curve-like change, with a turning point at a WSR of 2,500 s−1. The number of thrombi, the average fluorescence intensity and the area per thrombus showed similar trends, with an initial upwards incline followed by a decline. The thrombi formed at higher WSRs had a thicker shell, which led to a more densely packed core. Platelet thrombus formation under shear-flow was regulated by the adhesive strength, which was mediated by receptor-ligand interaction, the platelet deposition induced by shear rates and the detachment by the dynamic force of flow. This resulted in a balance between thrombus attachment, including adhesion and aggregation, and detachment. Collectively, compared with physiological low WSRs, pathological high WSRs caused thicker and more easily shed thrombi with more condensed cores, which was regulated by an attachment-detachment balance. These results provide novel insights into the properties of thrombus formation on collagen at different WSRs, and offers possible explanations for certain clinical physiopathological phenomena, including physical hemostasis and pathological thrombosis.