Skirgaudas M, Awad I A, Kim J, Rothbart D, Criscuolo G
Neurovascular Surgery Program, Yale University School of Medicine, New Haven, Connecticut, USA.
Neurosurgery. 1996 Sep;39(3):537-45; discussion 545-7. doi: 10.1097/00006123-199609000-00021.
Little is known about the biological mechanisms associated with the genesis, growth, and rupture of intracranial saccular aneurysms. It is postulated that the vascular wall pathological response of aneurysmal disease is associated with abnormal angiogenesis factor expression.
We have examined the expression and distribution of immunoreactivity to angiogenesis growth factors (vascular endothelial growth factor and basic fibroblast growth factor) and selected vascular wall matrix proteins (fibronectin, Type IV collagen, and alpha smooth muscle actin) in the walls of human intracranial aneurysms from surgical biopsy or autopsy specimens. Double antibody immunohistochemical stains were performed in contiguous fixed sections from three control circle of Willis arteries, five berry aneurysms, four giant aneurysms, and one mycotic aneurysm (three unruptured and seven ruptured lesions).
The aneurysmal wall exhibited diffuse disorganized expression of matrix proteins as compared to their organization in control vessels. There was strong patchy expression of vascular endothelial growth factor within the walls of all aneurysms, including marked staining of capillaries and small vessels within the thickened walls of giant lesions. The expression of basic fibroblast growth factor was more diffuse and occurred around the fibrocytes and myocytes within the disrupted media of 9 of 10 aneurysms.
These results confirm the gross architectural molecular disruption in the walls of intracranial aneurysms and illustrate an apparent biological response involving angiogenesis factors. Further research should elucidate the time course and possible causal relationships of these changes to aneurysm growth and rupture with the aim of possible therapeutic manipulation.
关于颅内囊状动脉瘤的发生、生长及破裂相关的生物学机制，目前所知甚少。据推测，动脉瘤性疾病的血管壁病理反应与异常的血管生成因子表达有关。
我们检测了手术活检或尸检标本中人类颅内动脉瘤壁上血管生成生长因子（血管内皮生长因子和碱性成纤维细胞生长因子）以及选定的血管壁基质蛋白（纤连蛋白、IV型胶原和α平滑肌肌动蛋白）的免疫反应性表达及分布情况。对取自三根 Willis 动脉环对照血管、五个浆果状动脉瘤、四个巨大动脉瘤和一个霉菌性动脉瘤（三个未破裂及七个破裂病变）的连续固定切片进行了双抗体免疫组织化学染色。
与对照血管中的组织结构相比，动脉瘤壁呈现出基质蛋白的弥漫性紊乱表达。在所有动脉瘤壁内均有血管内皮生长因子的强烈斑片状表达，包括巨大病变增厚壁内毛细血管和小血管的显著染色。碱性成纤维细胞生长因子的表达更为弥漫，在10个动脉瘤中9个的中膜破坏区域内的纤维细胞和肌细胞周围出现。
这些结果证实了颅内动脉瘤壁存在明显的结构分子破坏，并显示出涉及血管生成因子的明显生物学反应。进一步的研究应阐明这些变化与动脉瘤生长和破裂的时间进程及可能的因果关系，以期进行可能的治疗干预。
