血流动力学影响动脉瘤壁重构对颅内动脉瘤破裂的作用和机制

项目名称： 血流动力学影响动脉瘤壁重构对颅内动脉瘤破裂的作用和机制

项目编号： No.81471210

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王硕

作者单位： 首都医科大学

项目金额： 70万元

中文摘要： 颅内动脉瘤破裂与血流动力学和动脉瘤壁重构密切相关。我们前期发现破裂动脉瘤存在大量炎性细胞浸润，伴金属基质蛋白酶（MMPs）异常表达增高，并且动脉瘤壁面切应力分布不同，推测动脉瘤破裂是通过特定血流动力刺激动脉瘤壁细胞，这些细胞分泌细胞因子，促进瘤壁进行性重构来实现。该课题应用生物力学映射技术关联动脉瘤流体力学与分子病理来验证该假设，阐释具体机制。实验拟收集手术治疗的破裂与未破裂动脉瘤三维影像数据，以建立患者特定的流固耦合血流动力学模型，模拟两组动脉瘤几何形态相关的血流动力学参数，分析动脉瘤破裂的血流动力学机制；然后，取部分瘤壁进行蛋白组学筛选动脉瘤破裂的特异蛋白，部分瘤壁进行病理组织学研究，将动脉瘤血流动力学参数分布图与瘤壁免疫荧光图像数字融合，研究血流动力学影响动脉瘤壁进行性重构的作用，进一步筛选和验证动脉瘤破裂的分子机制，为预防或延缓动脉瘤破裂提供新的干预靶点，降低动脉瘤破裂的风险。

中文关键词： 颅内动脉瘤；血流动力学；管壁重构；破裂机制；分子机制

英文摘要： Hemodynamic factors and wall remodeling of aneurysm have been associated with rupture of cerebral aneurysms. Ruptured cerebral aneurysm is characterized significant loss of internal elastic lamina, increased inflammation reaction, large loss of smooth muscle cells in our previous studies, and aneurysm also has low wall shear stress and complex mechanical prameters. We suspect that aneurysmal wall cell transduces stimuli of hemodynamic forces into biochemical signals, which modulate secretion of cytokines and exacerbate progressing wall remodeling, leading to wall weakness and final rupture. Hemodynamics-biology co-mapping technique enables in the connection between the specific hemodynamic microenvironment and vascular remodeling. In this study, geometric parameters of ruptured aneurysm are assessed based on three dimensional digital subtraction angiographic images. These images are used to perform patient-specific computational fluid-structure interaction simulation. Meanwhile, one segment of aneurysm wall is analyzed by Protein microarray analysis, and other segement is obtained for immunohistochemistry and immunofluorescence staining. Furthermore, the hemodynamic field inside aneurysm is virtually sectioned based on the histological slicing planes. Simulative fluid images are digitally co-mapped with histological images. The connection of mechanical stimuli and vascular remodeling will be determined, and molecular mechanism underlying rupture of aneurysm will be also recognized. This study provides a new target biomarker for potential interventinal strategy to prevent aneruysm from rupturing.

英文关键词： Cerebral Aneurysm;Hemodynamics;Wall Remodeling;Rupture Mechanism;Molecular mechanism