以醣皮質類固醇治療大鼠腦出血對血腦屏障的影響

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Title:	以醣皮質類固醇治療大鼠腦出血對血腦屏障的影響 The effects of dexamethasone treatment on blood-brain barrier of brain in intracerebral hemorrhage rat
Authors:	郭佳惠 Chia-Hui Kuo
Contributors:	沈國愉楊仁宗嘉南藥理科技大學：生物科技研究所
Keywords:	腦內出血基質金屬蛋白酶 Matrix metalloproteinases Intracerebral hemorrhage
Date:	2007
Issue Date:	2008-12-03 11:18:36 (UTC+8)
Abstract:	腦內出血是一個快速變化且不易診斷的疾病，往往在幾個小時或幾天之內有急速的變化。但目前腦內出血後的腦部變化並無清楚的機制。基質金屬蛋白酶是一個內含鋅的蛋白酶家族，可分解基底層及細胞外間質。目前有些研究指出腦內出血後第二型和第九型基質金屬蛋白酶的產生是有害的，但其活性的多寡與對腦部的二次傷害是否有關尚未釐清。而內皮細胞黏附因子在受傷時會產生，可吸附白血球並且活化使血腦屏障通透性變高白血球易進入腦部中，為發炎反應的重要指標。在本實驗中我們採用以膠原蛋白分解酶誘導大鼠腦出血的動物模式來探討第二型和第九型基質金屬蛋白酶及內皮細胞黏附因子的表現，並且以免疫組織化學染色法和西方墨點分析來印證其表現量。在實驗中採用廣泛使用的抗發炎藥物-類固醇 (15 mg/kg) 來治療，看是否能抑制第二型和第九型基質金屬蛋白酶及內皮細胞黏附因子的表現量及減少腦水腫的程度。最後，結果發現第二型和第九型基質金屬蛋白酶及內皮細胞黏附因子可能在腦出血後扮演了有害的角色，使用類固醇可以抑制此兩者基質金屬蛋白酶及內皮細胞黏附因子的表現及腦水腫，或野i以減少腦出血後的二次傷害。 Intracerebral hemorrhage (ICH), an acute neurological disorder, has a rapidly evolving process that may progress over hours and days. The mechanisms of brain insult after ICH remain to be clarified. Matrix metalloproteinases (MMPs) is a family of zinc-dependent proteases which are involved in the degradation of basal lamina and extracellular matrix components. Although a few studies suggested a detrimental role of MMP-2 and MMP-9 in ICH, the relationships between it’s activity and the secondary brain changes after ICH are not determined. The intercellular adhesion molecule-1 (ICAM-1) binds to its leukocyte ligands and allows activated leukocytes entry into the CNS. In this study, we examine the expression of MMP-2, MMP-9 and ICAM-1 in vivo using a collagenase-induced rat model of ICH. Immunohistochemistry and Western blot revealed that MMP-2, MMP-9 and ICAM-1 was upregulated after ICH. The treatment with a broad-spectrum inflammation inhibitor dexamethasone (DEX) (15 mg/kg) could cause a decrease of MMP-2, MMP-9 and ICAM-1 expression and local neutrophil infiltration, then prevented the neuron death. The block of local brain edema around ICH was also observed. In conclusion, MMP-2, MMP-9 and ICAM-1 play a deleterious role in acute brain injury after ICH. The inhibition of MMP-2, MMP-9 and ICAM-1 expression with DEX during this critical period may be useful in treatment of secondary brain edema, which could be a therapeutic strategy for ICH.
Relation:	校內一年後公開，校外永不公開
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Dissertations and Theses

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