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研究生:劉妍穎
研究生(外文):Yen-Yin Liu
論文名稱:探討預先處理Baicalein對於甲基安非他命引發小白鼠紋狀體多巴胺系統神經毒害之研究
論文名稱(外文):Reversing the Methamphetamine-induced Striatal Dopaminergic Neurotoxicity in Mice via Pretreatment with Baicalein
指導教授:葉本和潘懷宗潘懷宗引用關係
指導教授(外文):Pen-Ho YehWynn H. T. Pan
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:67
中文關鍵詞:甲基安非它命一氧化氮多巴胺紋狀體黃芩苷神經毒害
外文關鍵詞:methamphetaminenitric oxidedopaminestriatumBaicaleinneurotoxicity
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Baicalein (5,6,7-trihydroxyflavone) 是中藥Scutellaria baicalensis Georgi黃芩主要成分之一,目前已發現其具有抗氧化、抗發炎以及抗腫瘤等多項作用。在使用高劑量的甲基安非他命之後,會導致氧化壓力、產生自由基,進而引發多巴胺神經系統神經毒害現象。因此,本實驗的目的在探討Baicalein是否可以藉由阻止多巴胺的耗損與調節一氧化氮(nitric oxide, NO)的表現,以減緩甲基安非他命所造成的神經毒害。實驗利用雄性ICR小白鼠,於一天之內每隔二小時經由腹腔注射(intraperitoneal; i.p.)分別給予一針甲基安非他命(5 mg/kg)或saline共注射4次,並於注射前30分鐘注射baicalein(1 mg/kg)。實驗動物於注射完最後一針算起的第1、第24小時,和第3天後斷頸犧牲,並取出小白鼠腦中的紋狀體(striatum)核區,分別進行多巴胺以及NO的濃度測試。結果顯示甲基安非他命會造成紋狀體內多巴胺含量下降與延緩NO的形成,而baicalein顯著的逆轉甲基安非他命造成多巴胺耗損的現象,並且在3天後baicalein仍可以將腦中紋狀體NO的含量維持在高濃度下。綜合實驗結果,推測baicalein可能透過NO來逆轉甲基安非他命造成紋狀體中多巴胺含量的下降。
Baicalein (5,6,7-trihydroxyflavone), one of the major constituents from the root of a Chinese medicinal herb Scutellaria baicalensis Georgi, has been found to have anti-oxidative, anti-inflammatory, and antitumor actions. The dopaminergic neurotoxicity after administration of high dose methamphetamine (METH) is believed to be the result of oxidative stress and generation of free radicals. This study evaluated whether baicalein is effective in preventing METH-induced depletion of striatal dopamine through modulating nitric oxide (NO) production. Male ICR mice were given four injections of METH (5 mg/kg, i.p.) or saline at 2 h intervals and/or treated with baicalein (1 mg/kg, i.p.) 30 min before each injection. Levels of dopamine and nitrate were measured separately in the striatum 1h, 24h and 3 days after METH-administration. Our data showed that METH caused striatal dopamine depletion and elicited a delayed production of NO. The pretreatment of baicalein significantly attenuated the METH-induced dopaminergic neurotoxicity, and a large amount of NO was found 3 days after co-injection of METH and baicalein. These results suggest that a possible role for NO modulates DA depletion and baicalein might be a potential candidate for the prevention of the neurological disorders evoked by METH abuse.
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