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研究生:許容瑄
研究生(外文):HSU,JUNG-HSUAN
論文名稱:Eupafolin 抑制紅藻氨酸誘導大鼠癲癇和海馬迴神經細胞死亡
論文名稱(外文):Eupafolin inhibits kainic acid-induced seizures and hippocampal cell death in rats
指導教授:王素珍王素珍引用關係
指導教授(外文):WANG, SU-JANE
口試委員:洪啓峯方嘉佑
口試委員(外文):HUNG, CHI-FENGFANG, JIA-YOU
口試日期:2021-07-28
學位類別:碩士
校院名稱:輔仁大學
系所名稱:生物醫學暨藥學研究所碩士班
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2021
畢業學年度:109
語文別:中文
論文頁數:54
中文關鍵詞:Eupafolin癲癇麩胺酸紅藻氨酸興奮性毒性
外文關鍵詞:Eupafolinepilepsyglutamatekainic acidexcitotoxicity
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  癲癇是一種常見的腦部疾病,台灣約有15萬人罹患此病,但目前抗癲癇藥物卻伴隨許多副作用,像是體重增加、牙齦出血、毛髮增多等等,所以開發安全且有效的新藥物是很重要的。Eupafolin 是一種黃酮類化合物,在大腦中eupafolin具有抑制谷氨酸釋放的能力。由於大量glutamate導致的興奮性毒性和癲癇的病變有關,因此我們利用glutamate類似物KA誘導癲癇的動物模式去探討eupafolin是否具有抗癲癇的作用。老鼠是先腹腔注射eupafolin 30分鐘後再腹腔注射KA,結果發現,eupafolin 可以減輕 KA 所誘導的癲癇、海馬迴中谷氨酸上升以及神經元退化,此外,eupafolin 還增加了大鼠海馬迴中磷酸化蛋白激酶C α(p-PKCα)、磷酸化-AMPA受體1(p-GluR1 )、wnt1、磷酸化蛋白激酶 B (p-AKT)、磷酸化糖原合酶激酶-3β (p-GSK-3β)、Bcl-2和β-catenin的表達。這些結果證明eupafolin在KA誘導癲癇的動物表現抗癲癇及神經保護作用是經由上調PKCα/GluR1 和 wnt/β-catenin途徑所致。此研究顯示eupafolin或許具有治療癲癇的發展潛力。
  Epilepsy is a chronic brain disease that has been estimated to affect about 150000 people in Taiwan. The use of antiepileptic drugs is the primary therapy for treating epilepsy. However, current antiepileptic drugs have numerous adverse effects. Accordingly, the discovery of a novel antiepileptic drug with better efficacy and fewer side effects is of importance. Natural products from herbs have contributed significantly in antiepileptic drug discovery. Eupafolin is a flavonoid compound, and has glutamate release-inhibiting activity in the brain. Given the involvement of excitotoxicity caused by massive glutamate in the pathophysiology of epilepsy, we explored the antiepileptic effect of eupafolin and compared with clinical drug carbamazepine (CBZ) in kainic acid (KA)-induced seizures in rats. Rats were intraperitonal injected with eupafolin (10 or 50 mg/kg) or CBZ (50 mg/kg) 30 min before KA (15 mg/kg) intraperitoneal injected. Our results revealed that eupafolin attenuated KA-induced seizure activity, glutamate elevation, and neuronal death in the hippocampus. Furthermore, eupafolin increased phospho Protein Kinase C alpha (p-PKCα), Phospho-AMPA Receptor 1(p-GluR1), wnt1, phosphorylated-protein kinase B (p-AKT), phosphorylated-glycogen synthase kinase-3β (p-GSK-3β), Bcl-2, and β-catenin expression in the hippocampus of KA-treated rats. These results demonstrate that eupafolin exert its antiepileptic and neuroprotective actions in KA-treated rats through the upregulation of PKCα/GluR1 and wnt/β-catenin signaling. Therefore, the present study suggests that eupafolin is the potentially useful in the prevention of epilepsy.
第一章 前言 1
第二章 文獻探討 2
一、 、癲癇 2
二、 Eupafolin 3
三、 麩胺酸(glutamate) 5
四、 興奮性神經毒性之動物模式 7
第三章 材料與方法 8
一、 試劑 8
二、 動物實驗 8
三、 動物行為模式 9
四、 腦電波分析 9
五、 以高效液相色譜法分析確定海馬迴麩胺酸含量 10
六、 腦組織切片製備 11
七、 中性紅染色 11
八、 Fluoro-Jade B 染色 12
九、 西方墨點法 12
十、 統計分析 13
第四章 實驗結果 14
一、 Eupafolin可降低紅藻氨酸大鼠癲癇行為以及大鼠海馬迴麩胺酸濃度的增加 14
二、 Eupafolin可降低紅藻氨酸大鼠的海馬迴神經細胞損傷 15
三、 Eupafolin可提升紅藻氨酸大鼠之海馬迴p-PKCα與p-GluR1表達量 15
四、 Eupafolin可提升紅藻氨酸大鼠之海馬迴wnt1表達量 16
五、 Eupafolin可提升紅藻氨酸大鼠之海馬迴p-Akt、p-GSK-3β表達量 17
六、 Eupafolin可提升紅藻氨酸大鼠之海馬迴β-catenin、Bcl-2表達量 18
第五章 討論 19
第六章 結論 22
第七章 參考文獻 40


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