本文關(guān)鍵詞：顱內(nèi)動脈瘤動物模型建立及發(fā)病機制的研究　出處：《四川大學》2005年博士論文　論文類型：學位論文

  更多相關(guān)文章： 顱內(nèi)動脈瘤 發(fā)病機制 CD68 c-Jun MMP-9 動物模型 改良入路

【摘要】：血管壁細胞外基質(zhì)的大量破壞是顱內(nèi)動脈瘤形成的重要因素,而細胞外基質(zhì)的破壞與基質(zhì)金屬蛋白酶(matrix metalloproteinase,MMPs)尤其MMP-9過度表達密切相關(guān),同時伴有MMP的抑制劑(tissue inhibitor of metalloproteinase,TIMP)表達升高,但二者的平衡失調(diào)致使MMP-9的超量表達參與了顱內(nèi)動脈瘤的發(fā)生及其發(fā)展。 巨噬細胞作為重要的炎癥分子通過誘導MMP-9的表達參與了腹主動脈瘤的形成,CD68作為巨噬細胞的分子標志常用于判斷組織內(nèi)炎癥反應(yīng)的程度。此外研究表明MMP-9的過度表達與轉(zhuǎn)錄因子c-Jun有關(guān),本研究擬探討誘導顱內(nèi)動脈瘤血管壁內(nèi)MMP-9的過度表達相關(guān)調(diào)控機制,從顱內(nèi)動脈瘤MMP-9誘導產(chǎn)生的早期階段阻斷其后繼病理反應(yīng),為臨床開發(fā)新藥或檢測特異性病理分子標記物提示顱內(nèi)動脈瘤形成早期提供有用的實驗依據(jù)。 自Hashimoto首次運用結(jié)扎大鼠一側(cè)頸總動脈+切除一側(cè)腎臟+術(shù)后(高鹽飲食+β-丙晴氨)喂養(yǎng)2月等綜合措施成功建立顱內(nèi)動脈瘤動物模型后,該模型幾經(jīng)改進和完善,發(fā)現(xiàn)腎性高血壓和血流動力學異常是制作顱內(nèi)動脈瘤發(fā)病機制模型的兩大基本條件,制作的動物模型與人類
[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

【學位授予單位】：四川大學
【學位級別】：博士
【學位授予年份】：2005
【分類號】：R-332;R739.41

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