计算流体力学结合病理学对颅内动脉瘤生长及破裂机制的研究

发布时间：2018-03-23 23:38

本文选题：血流动力学　切入点：颅内动脉瘤　出处：《中国人民解放军医学院》2015年博士论文

【摘要】：第一部分未破裂颅内动脉瘤血流动力学与组织病理学分析目的：利用计算流体力学研究未破裂动脉瘤血流动力学特征,同时行动脉瘤标本的组织病理学检测,分析血流动力学各项参数所对应的动脉瘤病理损伤过程, 进一步阐明血流动力学和病理损伤在颅内动脉瘤发生和生长的作用机理。方法：收集8例经开颅手术夹闭并切除动脉瘤的未破裂颅内动脉瘤患者的资料,采用Mimics17.0软件进行重建三维实体模型,应用Ansys14.5软件进行三维流固耦合模拟,分析相关的力学参数(壁面剪切力(WSS)、范-米斯氏压力、总压力、流体流线和变形程度)特征,将这些参数的最高值、最低值所处的位置与手术得到的实体标本对应起来。应用3D打印技术打印模型,使标本得到最大程度的复原。用免疫组织化学方法检测这些部位的动脉瘤壁白细胞介素-1β(IL-1β)、肿瘤坏死因子-a (TNF-α)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、诱导型一氧化氮合酶(iNOS)和内皮型一氧化氮合酶(eNOS)的表达。结果：动脉瘤壁压力呈不均匀分布,但差别不大；WSS一般在瘤颈处最大,瘤体和瘤顶较低；范-米斯氏压力呈现不均匀分布,瘤颈处相对于瘤顶处大。在WSS、范-米斯氏压力、总压力和变形程度最大值和最小值区域,都可见到IL-1β、 TNF-α、MMP-2、MMP-9、iNOS表达,且两者之间没有统计学差异(P0.05);在高WSS区域eNOS表达明显比低WSS区域多,两者之间有统计学意义(P0.05)；而在范-米斯氏压力、总压力和变形程度最大值和最小值区域,都可见eNOS表达,且两者之间没有统计学差异(P0.05)。结论：IL-1β、TNF-α、MMP-2、MMP-9、iNOS、eNOS都在颅内动脉瘤的发生和发展中起到作用,高WSS可能通过促进eNOS表达上调,进而导致动脉瘤发生和进展。第二部分破裂颅内动脉瘤血流动力学及组织病理学分析目的：利用计算流体力学研究破裂动脉瘤血流动力学特征,同时行动脉瘤标本的组织病理学检测,分析流体力学各项参数所对应的动脉瘤病理损伤过程,进一步阐明血流动力学和病理损伤在颅内动脉瘤破裂中的作用机理。方法：收集10例经开颅手术夹闭并切除动脉瘤的破裂颅内动脉瘤患者的资料,采用Mimics17.0软件进行重建三维实体模型，应用Ansys14.5软件进行三维流固耦合模拟,分析相关的力学参数(WSS、范-米斯氏压力、总压力、流体流线和变形程度)特征。应用3D打印技术打印模型,使标本得到最大程度的复原。用免疫组织化学方法检测动脉瘤破裂处及瘤体处的IL-1β、TNF-α、MMP-2、MMP-9、iNOS和eNOS的表达。结果：8例破裂处位于动脉瘤顶处(80%),2例位于瘤体处(20%)；破裂处多位于低WSS、高压力区域；在破裂处与瘤体处都能见到IL-1β、TNF-α、MMP-2、 MMP-9、iNOS和eNOS的表达,但破裂处的IL-1p和TNF-α的表达明显比瘤体处多,两者有统计学意义(P0.05)。结论：动脉瘤破裂处多位于低WSS及高压力处,而与范-米斯氏压力及壁变形程度无直接相关；低WSS可能通过IL-1β、TNF-α等炎性因子促进动脉瘤壁炎症反应,细胞外基质蛋白降解,最后导致动脉瘤破裂。
[Abstract]:The first part of unruptured intracranial aneurysm hemodynamics and histopathology analysis objective: using computational fluid mechanics research features of unruptured aneurysm artery hemodynamics, and pathological action vein tumor specimens, detection, analysis of corresponding parameters of the blood flow dynamics dynamic process of vein tumor pathological damage, further clarify the hemodynamics and pathological injury in brain aneurysm formation and growth mechanism. Methods: the data of 8 patients with craniotomy clipping and resection of aneurysms of unruptured intracranial aneurysm patients, re built three-dimensional solid model by using Mimics17.0 software, Ansys14.5 software was used to analyze the three-dimensional fluid solid coupling simulation, mechanical analysis of relevant parameters (the wall shear stress (WSS), van mees's pressure, total pressure, fluid flow and deformation degree) characteristics, the highest values of these parameters, the minimum value of the position and Operation of specimen correspond. Application of 3D printing technology to print model, make the specimen to obtain the greatest degree of aneurysm restoration. IL-2 was detected by immunohistochemical method in these parts of the -1 beta (IL-1 beta), tumor necrosis factor -a (TNF- alpha), matrix metalloproteinase -2 (MMP-2), matrix metalloproteinase -9 (MMP-9), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expression. Results: the aneurysm wall pressure distribution was uneven, but the difference was not significant; the maximum WSS in the neck of aneurysms, aneurysm dome and roof is low; van mees's pressure appears not uniform distribution of aneurysm neck tumors compared to large at the top. In WSS, van mees's pressure, total pressure and deformation degree of maximum and minimum area, can see IL-1 beta, TNF- alpha, MMP-2, MMP-9, iNOS expression, and there was no significant difference between them (P0.05); in the high WSS region eNOS WSS expression was significantly lower than the area, there were significant differences between two groups (P0.05); while in the van mees's pressure, total pressure and deformation degree of maximum and minimum area, visible expression of eNOS, and there was no significant difference between them (P0.05). Conclusion: IL-1 beta, TNF- alpha, MMP-2, MMP-9, iNOS and eNOS in the occurrence and development of intracranial aneurysms in high WSS may play a role, by promoting the expression of eNOS, which leads to the aneurysm occurrence and progression. The second part of the ruptured aneurysm intracranial hemodynamics and tissue pathological analysis objective: using computational fluid dynamics study on rupture characteristics of tumor artery hemodynamics, and the pathological action aneurysm specimen examination, analysis of pathological injury of aneurysm of corresponding parameters of fluid mechanics, to further clarify the mechanism of hemodynamics and pathological injury in intracranial aneurysm rupture in side. Method: collect 10 cases of patients with ruptured intracranial aneurysms after craniotomy clipping and resection of aneurysms of the reconstructed 3D model data, using Mimics17.0 software, Ansys14.5 software was used to analyze the three-dimensional fluid solid coupling simulation, mechanical analysis of related parameters (WSS, van Meese's pressure, total pressure, fluid flow and deformation degree) characteristics. The application of 3D printing technology to print model, make the specimen get maximum recovery. Immunohistochemistry was used to detect the aneurysm rupture and aneurysm of the IL-1 beta, TNF- alpha, MMP-2, MMP-9, iNOS and eNOS expression. Results: 8 cases of ruptured aneurysms located at the top (80%). In 2 cases (20%); Department of tumor rupture in low WSS, high pressure in the region; rupture and aneurysm could be seen IL-1 beta, TNF- alpha, MMP-2, MMP-9, iNOS and eNOS expression, but the expression of IL-1p and TNF- alpha rupture than tumor at. Two Have statistical significance (P0.05). Conclusion: the office located in low WSS and high pressure at the ruptured aneurysm, and van mees's pressure and wall deformation degree is not directly related to low WSS; through IL-1 beta, TNF- alpha and other inflammatory factors promote the aneurysm wall inflammation, extracellular matrix protein degradation. Finally lead to aneurysm rupture.

【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R651.12

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