A new unsteady three-dimensional convective-diffusive mathematical model for the transportation of macromolecules and water across the arterial wall was proposed . After the formation of leaky junctions due to the mit...A new unsteady three-dimensional convective-diffusive mathematical model for the transportation of macromolecules and water across the arterial wall was proposed . After the formation of leaky junctions due to the mitosis of endothelial cell of the arterial wall, the macromolecular transport happens surrounding the leaky cells. The arterial wall was divided into four layers: the endothelial layer, the subendothelial intima, the internal elastic lamina and the media for the convenience of research. The time-dependent concentration growth, the effect of the shape of endothelial cell and the effect of physiological parameters were analyzed. The analytical solution of velocity field and pressure field of water flow across the arterial wall were obtained; and concentration distribution of three macromolecules; LDL, HRP and Albumin, were calculated with numerical simulation method. The new theory predicts, the maximum and distribution areas of time dependent concentration with round-shape endothelial cell are both larger than that with ellipse-shape endothelial cell. The model also predicts the concentration growth is much alike that of a two-dimensional model and it shows that the concentration reaches its peak at the leaky junction where atherosclerotic formation frequently occurs and falls down rapidly in a limited area beginning from its earlier-time growth to the state when macromolecular transfer approaches steadily. These predictions of the new model are in agreement with the experimental observation for the growth and concentration distribution of LDL and Albumin.展开更多
随着科学技术的不断进步、替代毒理学的快速发展以及动物实验禁令在部分国家和地区的推广,传统风险评估的局限性日益凸显,下一代风险评估(next generation risk assessment,NGRA)应运而生。NGRA是一种替代动物实验的新型风险评估方法,...随着科学技术的不断进步、替代毒理学的快速发展以及动物实验禁令在部分国家和地区的推广,传统风险评估的局限性日益凸显,下一代风险评估(next generation risk assessment,NGRA)应运而生。NGRA是一种替代动物实验的新型风险评估方法,它依赖于通过体外测试、体外-体内外推(in vitro to in vivo extrapolation,IVIVE)、计算毒理学、交叉参照等新路线方法(new approach methodologies,NAMs)生成的数据,这些方法使用基于人类的模型,准确地反映了人类生物学,增加了风险评估的准确性以及高效性。本文系统整理了NGRA的研究现状和进展,简要介绍了NGRA的框架,主要围绕NGRA采用的NAMs及面临的挑战进行了重点分析,同时分享多种暴露场景下的应用案例,并对NGRA未来研究方向进行展望,以期为我国化学物质环境管理提供更好的方法学支撑。展开更多
文摘A new unsteady three-dimensional convective-diffusive mathematical model for the transportation of macromolecules and water across the arterial wall was proposed . After the formation of leaky junctions due to the mitosis of endothelial cell of the arterial wall, the macromolecular transport happens surrounding the leaky cells. The arterial wall was divided into four layers: the endothelial layer, the subendothelial intima, the internal elastic lamina and the media for the convenience of research. The time-dependent concentration growth, the effect of the shape of endothelial cell and the effect of physiological parameters were analyzed. The analytical solution of velocity field and pressure field of water flow across the arterial wall were obtained; and concentration distribution of three macromolecules; LDL, HRP and Albumin, were calculated with numerical simulation method. The new theory predicts, the maximum and distribution areas of time dependent concentration with round-shape endothelial cell are both larger than that with ellipse-shape endothelial cell. The model also predicts the concentration growth is much alike that of a two-dimensional model and it shows that the concentration reaches its peak at the leaky junction where atherosclerotic formation frequently occurs and falls down rapidly in a limited area beginning from its earlier-time growth to the state when macromolecular transfer approaches steadily. These predictions of the new model are in agreement with the experimental observation for the growth and concentration distribution of LDL and Albumin.
文摘随着科学技术的不断进步、替代毒理学的快速发展以及动物实验禁令在部分国家和地区的推广,传统风险评估的局限性日益凸显,下一代风险评估(next generation risk assessment,NGRA)应运而生。NGRA是一种替代动物实验的新型风险评估方法,它依赖于通过体外测试、体外-体内外推(in vitro to in vivo extrapolation,IVIVE)、计算毒理学、交叉参照等新路线方法(new approach methodologies,NAMs)生成的数据,这些方法使用基于人类的模型,准确地反映了人类生物学,增加了风险评估的准确性以及高效性。本文系统整理了NGRA的研究现状和进展,简要介绍了NGRA的框架,主要围绕NGRA采用的NAMs及面临的挑战进行了重点分析,同时分享多种暴露场景下的应用案例,并对NGRA未来研究方向进行展望,以期为我国化学物质环境管理提供更好的方法学支撑。
