【作者】 孙雷；

【导师】 林建忠；

【作者基本信息】 浙江大学 ， 流体力学， 2005， 博士

【摘要】 动脉血管壁内皮细胞与平滑肌细胞处于一个复杂的力学环境中，受到脉动的周向张应力、剪切应力、静压力等的综合作用。正常情况下，血管壁细胞的生长与物质合成、分泌处于微妙的动态平衡中，以维持血管壁的正常结构与生理功能，保证血液在血管中的正常流动。如果作用在血管壁细胞上的力发生很大变化，如高血压情况下，则细胞的生长与分泌功能被打乱，血管壁细胞特别是血管平滑肌细胞发生异常增殖，细胞外基质也异常增多，导致血管壁中膜增厚，平滑肌细胞向内膜迁移。血管平滑肌细胞的增殖在动脉粥样硬化性疾病的发展中起着重要作用，而高血压则是引起平滑肌细胞异常增殖的主要因素。 动脉粥样硬化性病变发生的位置具有特定性，好发于人体动脉血管的分枝、弯曲和狭窄处等血管几何形状发生急剧变化的部位。实验研究表明，血流动力学因素可以影响血管内皮细胞和平滑肌细胞的形态和功能、脂质的浓度极化和凝血系统等等。血浆脂蛋白在血管壁内的沉积是动脉粥样硬化过程中的初发事件，脂蛋白向血管壁内渗透与传输很大程度上取决于脂蛋白在动脉血管壁表面的浓度，浓度越高，渗入血管壁内的脂蛋白越多。 首先，为了研究静压力对细胞生长的影响，本文的实验利用体外培养的植有牛主动脉血管内皮细胞与平滑肌细胞的膨化聚四氟乙烯人工血管，考察在不同的压力下(0，80，100与120mmHg)与不同的初始细胞种植密度下(1×10~6 cells／cm~2与2×10~6 cells／cm~2)培养7天后细胞的生长与分泌情况，发现80，100与120mmHg的静压力均会引起平滑肌细胞的增殖与Ⅳ型胶原分泌的增加。不同的初始细胞种植密度也对人工血管上细胞的生长有影响，当初始种植密度加倍时，常压与100mmHg压力下培养19天后细胞层的厚度均增加了5倍多。 其次，为了研究血流动力学因素对血管内皮细胞与平滑肌细胞生长的影响，本文建立了利用直管与扩张管的灌流实验装置，考察不同的流动状态对植有牛主动脉血管内皮细胞与平滑肌细胞的膨化聚四氟乙烯人工血管上细胞组织生长的更多还原

【Abstract】 The blood vessel cells in vivo are subjected in complicated circumferential stress, flow shear stress and pressure, etc., and those stresses are changing with the pulstile flow of blood. Abnormal changes in stretch usually instigate adaptive vascular remodeling, including abnormal growth and proliferation of vascular smooth muscle cells as well as extracellular matrix. High blood pressure (hypertension) is implicated to be a crucial reason for the blood vessel remodeling and thus is the main cause of atherosclerosis.Lesions of atherosclerosis are always observed at certain parts of the arterial system, such as curves or bifurcations, where the blood flow is disturbed, causing much lower or higher wall shear stress. That will affect the function of blood vessel cells and the deposition of blood plasma lipoproteins as well. It has been proved that blood plasma lipoproteins, especially the low density lipoprotein (LDL), play an important role in the development and progress of atherosclerosis, and LDL uptake by cells is mostly depended on the concentration of the deposited LDL particles on the vessel wall.In the first part, we used bovine aortic endothelial cells (EC) and smooth muscle cells (SMC) co-cultured ePTFE vascular grafts with different original cell seeding densities subjected to 0 (as a control), 80, 100 and 120mmHg hydrostatic pressure for 7 days, and the increase of cell layer thickness under high pressure was observed. It was concluded that moderately high pressure resulted in cell proliferation and increase of collagen type IV synthesis of the cells on ePTFE vascular grafts. When the original cell seeding density doubled, the thickness of cell layer increased dramatically after 19 days culture (ever since SMC seeding) under the pressure of both 0 and 100mmHg.In the second part, we examined different flow conditions on the cell growth of EC-SMC co-cultured ePTFE vascular graft by using expended and non-expended circular tube flow apparatus. After 7 days flow, we found that the cells exposed to更多还原