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  5. 薑黃素藉由調節星狀細胞表現與分泌RANTES 達成神經保護作用
 
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薑黃素藉由調節星狀細胞表現與分泌RANTES 達成神經保護作用

Other Title
Curcumin neuroprotection via regulation of RANTES expression and secretion from astrocytes
Type
thesis
Date Issued
2011-01-27
Author(s)
林牧熹
Advisor
邱文達
Subjects
系所名稱:臨床醫學研究所
Description
學位別:博士
語文別:英文
指導教授:邱文達
共同指導教授:李怡萱;洪國盛
口試委員:洪慶章;陳子勇;盧星華;張承仁
中文關鍵字:薑黃素;星狀細胞;RANTES;神經保護作用;脊髓損傷
Abstract
薑黃素已廣泛應用於神經發炎和神經退化性疾病之治療,如急性脊髓傷害期間之炎症反應。之前脊髓損傷研究中已證明,在此種急性疾病傷害期間,薑黃素抑制了細胞凋零和神經細胞的死亡,降低了星狀細胞再次激活化。我們觀察到薑黃素能降低了GFAP的表現,也就是說薑黃素能降低星狀細胞再次激活化。薑黃素對神經元之保護作用可以歸因於薑黃素的抗發炎作用。The expression of regulated on activation normal T expressed and secreted (RANTES) 屬於CC趨化因子家族 (chemokine) 中的一員,在脊髓及腦部之神經發炎反應中扮演著非常重要的角色。文獻上也揭示在神經發炎反應其中之驅化因子,如RANTES,具有「雙面效益(double-edged sword effect)」:除了會惡化發炎反應的進行之外,在生理反應適量濃度上,亦具有保護神經之作用。本篇論文主旨在進一步探討薑黃素藉由調節星狀細胞所分泌之RANTES達到神經保護作用的分子機轉。研究結果證實薑黃素可以降低傷害下星狀細胞所分泌之RANTES( injury-induced RANTES)。使用 siRANTES knockdown, lipopolysaccharide 傷害下星狀細胞所分泌的 RANTES 被大幅的減少,此傷害下之星狀細胞條件培養液之神經毒性,也大幅的降低。因此薑黃素對神經元之保護作用可以歸因於薑黃素降低傷害下星狀細胞所分泌之RANTES之作用。
而我們也同時發現薑黃素可以提升星狀細胞所分泌之RANTES (非傷害狀態)。使用siRANTES knockdown,星狀細胞所分泌的 RANTES 被大幅的減少,此星狀細胞條件培養液之神經保護作用,也會大幅的降低。因此薑黃素對神經元之保護作用可以歸因於薑黃素可以提升星形細胞所分泌之RANTES之作用。此研究成果正可應用在發展脊髓損傷及神經退化性疾病的治療策略提供了重要的學理依據。
URI
https://203.71.86.71/handle/123456789/13503

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