抗肿瘤血管生成治疗中血管正常化窗口期血液灌注数值模拟初探  

Numerical simulation of tumor blood perfusion in vascular normalization window period by anti-angiogenesis therapy

作　　者：刘方洁[1] 蔡彦[1] 许世雄[1] LONG Quan 张洪一[1] 曹金凤[1] 周瑜[1] 

机构地区：[1]复旦大学力学与工程科学系,上海200433 [2]Brunel Institute for Bioengineering, School of Engineering and Design, Brunel University, Uxbridge, Middlesex, UK

出　　处：《生物医学工程与临床》2010年第2期105-109,共5页Biomedical Engineering and Clinical Medicine

基　　金：国家自然科学基金资助项目(10772051);上海市重点学科建设项目(B112)

摘　　要：目的研究在抗血管生成因子——内皮抑制素(ES)作用下,血管正常化窗口期肿瘤血管渗透率变化对血液灌注的影响。方法数值模拟在ES作用下肿瘤血管正常化期过程中的血液灌注。设血液为不可压缩牛顿流体,肿瘤内间质流动遵循Darcy定律,管内流量用扩展的Poiseuille定律,跨壁流量采用Starling定律,以肿瘤血管渗透率表征血管正常化期肿瘤血管的变化。用差分迭代法数值计算肿瘤血液灌注组织间质压强。结果在ES作用下出现的"血管正常化窗口期",肿瘤毛细血管渗透率将下降,肿瘤组织间质高压降低,在肿瘤血管渗透率和正常血管一致时,肿瘤组织间质压强明显下降,压强梯度上升。此后肿瘤毛细血管渗透率上升,肿瘤组织间质压强又增高,压力梯度下降。结论ES不仅抑制了肿瘤血管生成,而且随肿瘤血管渗透率的变化,在"血管正常化窗口期"改善了肿瘤血液动力学环境,有利于其他治疗肿瘤药物的输运。抗肿瘤血管生成与其他方法联合可望有较好的疗效。Objective To study the effect of changing hydraulic permeability by anti-angiogenesis drug（endostatin,ES） on blood perfusion of solid tumors.Methods The blood perfusion of tumor by the action of ES during the＂vascular normalization window period＂was performed with numerical simulation.The blood was assumed as incompressible Newtonian flow and interstitial flow based on Darcy＇s law while vascular flow rate and transvascular flow rate abided by extended Poiseuille＇s law and Starling＇s law respectively.Hydraulic permeability of the vascular wall represented the change of tumor vasculature during the normalization period.Then,the interstitial pressure of tumor blood perfusion was calculated with differential iteration method.Results The interstitial pressure in tumor tissue domain decreased while the pressure gradient increased during the＂vascular normalization window period＂.Then the interstitial pressure increased and the pressure gradient decreased after the＂vascular normalization window period＂.Conclusion It is demonstrated that the ES not only inhibits tumor angiogenesis,but also improves the hemodynamic environment of tumor tissue in＂vascular normalization window period＂associating with the changes ofhydraulic permeability rate and in favor of transportation other antitumor drugs.Thus the application anti-angiogenesis therapy combined with other therapeutic approches can result in better curativeeffectontumor.

关 键 词：肿瘤 抗血管生成因子 内皮抑制素 血管正常化窗口期 渗透率 血液灌注 数值模拟 

分 类 号：R730.5[医药卫生—肿瘤]