颅内动脉瘤动物模型建立及发病机制的研究

发布时间：2017-12-31 17:08

本文关键词：颅内动脉瘤动物模型建立及发病机制的研究　出处：《四川大学》2005年博士论文　论文类型：学位论文

【摘要】：血管壁细胞外基质的大量破坏是颅内动脉瘤形成的重要因素,而细胞外基质的破坏与基质金属蛋白酶(matrix metalloproteinase,MMPs)尤其MMP-9过度表达密切相关,同时伴有MMP的抑制剂(tissue inhibitor of metalloproteinase,TIMP)表达升高,但二者的平衡失调致使MMP-9的超量表达参与了颅内动脉瘤的发生及其发展。巨噬细胞作为重要的炎症分子通过诱导MMP-9的表达参与了腹主动脉瘤的形成,CD68作为巨噬细胞的分子标志常用于判断组织内炎症反应的程度。此外研究表明MMP-9的过度表达与转录因子c-Jun有关,本研究拟探讨诱导颅内动脉瘤血管壁内MMP-9的过度表达相关调控机制,从颅内动脉瘤MMP-9诱导产生的早期阶段阻断其后继病理反应,为临床开发新药或检测特异性病理分子标记物提示颅内动脉瘤形成早期提供有用的实验依据。自Hashimoto首次运用结扎大鼠一侧颈总动脉+切除一侧肾脏+术后(高盐饮食+β-丙晴氨)喂养2月等综合措施成功建立颅内动脉瘤动物模型后,该模型几经改进和完善,发现肾性高血压和血流动力学异常是制作颅内动脉瘤发病机制模型的两大基本条件,制作的动物模型与人类
[Abstract]:The destruction of a large number of vascular extracellular matrix is an important factor for the formation of intracranial aneurysms, and the destruction of the extracellular matrix and matrix metalloproteinases (matrix, metalloproteinase, MMPs) especially over expression of MMP-9 is closely related with MMP (tissue inhibitor and inhibitor of metalloproteinase, TIMP) expression increased, but the two imbalance resulting in excess the expression of MMP-9 is involved in the occurrence and development of intracranial aneurysm.
As an important form of macrophage inflammatory molecules involved in abdominal aortic aneurysm by inducing the expression of MMP-9, CD68 as a molecular marker of macrophage inflammatory response is used to judge within the organization degree. Furthermore the study showed that the overexpression of MMP-9 related transcription factor c-Jun, this study intends to explore the induce over expression of intracranial aneurysms within the vascular wall of MMP-9 related control mechanism of early stage from MMP-9 intracranial aneurysm induced by blocking its subsequent pathological reaction, for the clinical development of new drugs or detection of specific pathological molecular markers suggest intracranial aneurysm formation to provide experimental basis for useful early.
Since Hashimoto first use of carotid artery ligation in rats after unilateral nephrectomy + + (high salt diet + beta C clear ammonia) comprehensive measures of feeding February successfully established the animal model of intracranial aneurysms after the model has been improved and perfected, found in renal hypertension and abnormal hemodynamics are the two basic conditions of production models of the pathogenesis of intracranial aneurysm, animal models and human production

【学位授予单位】：四川大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R-332;R739.41

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