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肝血窦独特物理结构调控白细胞迁移的数值模拟
英文题名Numerical simulation of leukocyte migration in the unique physical structure of hepatic sinusoids
刘也
导师吕守芹
2018-05-28
学位授予单位中国科学院大学
学位授予地点北京
培养单位中国科学院力学研究所
学位专业一般力学与力学基础
关键词耗散粒子动力学 肝血窦 白细胞迁移 物理/力学微环境
英文摘要

    肝脏是人体执行免疫防御的重要器官,而肝血窦是肝脏执行免疫防御的主要组织部位。与经典炎症级联反应不同,白细胞在肝血窦内呈现无滚动的“滞留”募集特征,但是其内在机制尚不清楚。肝血窦是具有狭窄的血窦内腔与血窦间隙两层流道,两层流道之间因为肝血窦内皮细胞表面分布大量筛孔而具有渗流,而且含有肝细胞、血窦内皮细胞、枯否氏细胞及肝卫星细胞等四种细胞共存的特殊结构,肝脏疾病的发生发展伴随着肝血窦结构的变化。目前有观点认为肝血窦复杂力学/物理微环境的协同作用是介导白细胞在肝血窦内“无滚动” 滞留的重要因素,但是尚无直接证据,而且肝血窦几何结构、 血流剪切、 两层流道间的渗透率等因素对细胞在肝血窦内的各自贡献如何也尚未报道。
    基于此,本论文采用耗散粒子动力学模拟方法,从力学物理角度系统考察了血窦管径、血流剪切、血窦内皮细胞表面空隙率以及细胞刚度与数量等因素对细胞迁移的调控作用。主要结论如下: 1)血窦管径大于细胞直径时,血流剪切是驱动细胞迁移的主要驱动力,细胞的迁移速度随流体剪切的增加而加快,血窦内腔孔隙率、窦间隙大小均会通过调控血窦内腔流体剪切的大小进而调控细胞的迁移。孔隙率或窦间隙越大,血窦内腔的流体剪切越小,细胞迁移速率越慢,反之呈相反趋势; 2)血窦管径小于细胞直径时,细胞因为受到血窦壁的约束其变形率大大增加,迁移速度显著降低。细胞刚度对其迁移影响不大; 3)非受限条件下,两细胞共存会显著降低其迁移速度,受限条件下则呈相反趋势。细胞间初始距离会随着模拟时间降低进而达到稳定值,当初始距离较低时,平衡后细胞会产生聚集现象。本工作为深入理解特殊肝血窦物理/力学微环境对白细胞在肝血窦内的募集作用提供线索。

 
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     The liver is an important organ for performing immune defenses, and this function is mainly carried out in the hepatic sinusoid. In contrast with the classic inflammatory cascade, the recruitment of leukocytes in hepatic sinusoids present the feature of retention without rolling, but its underlying mechanism is not yet clear. Hepatic sinusoids have both narrow sinusoidal lumen and disse space, and there is interstifial flow between the two-layered channel due to the existence of fenestrae cluster on the LSECs. And four types of hepatic cells, including LSECs, KCs, HSCs and HCs,coordinate simultaneously and precisely inside liver sinusoids. The typical structure of hepatic sinusoid will change significantly following the occurrence and development of hepatic diseases. By now, hepatic sinusoid is regarded as helping the “no rolling”retention of leukocytes upon its complicated mechanics/physical microenvironment,but still lacks direct evidence. Furthermore, their respective contribution of hepatic sinusoidal structure, blood flow, permeability between the two channels as well as cellular stiffness to the leukocyte’s recruitment has not been reported.
     Dissipative particle dynamics simulation method was used in this dissertation to investigate the impacts of sinusoidal diameter, blood flow, surface permeability of LSEC, cellular stiffness and number on leukocyte’s migration systematically. The main results are as followed: 1) Blood flow is the dominated driving force for cellular migration in the non-confined sinusoidal lumen, the migration velocity speeds up with the increase of shear stress, and the porosity and disse space size will regulate cell migration by regulating the flow of the sinusoidal lumen. The greater the porosity or disse space is, the slower flow shear stress in the sinusoidal lumen and corresponding cell migration are; 2) The cellular deformation increases, and migration velocity decreases significantly in the confined sinusoidal lumen. Cellular stiffness has negligible effect on its migration; 3) The coexistance of two cells significantly reduces their migration velocity contrast to that of single cell existence in the non-confined sinusoidal lumen, and the results in the confined channel exhibit the opposite trend.Distance between the two cells will reduce and reach to a stable value following the simulation time, and the two cells will aggregate together finally if their initial distance is set small enough. This work will give insight on the impact of unique physical/mechanical microenvironment of hepatic sinusoids on the recruitment of leukocytes.

语种中文
文献类型学位论文
条目标识符http://dspace.imech.ac.cn/handle/311007/73182
专题国家微重力实验室
作者单位中国科学院力学研究所
推荐引用方式
GB/T 7714
刘也. 肝血窦独特物理结构调控白细胞迁移的数值模拟[D]. 北京. 中国科学院大学,2018.
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