摘要 茶葉為山茶科 （Theaceae） 植物 Camellia sinensis （L.） O. KUNTZE 之葉。本研究以大鼠前中腦動脈及兩側頸總動脈結紮為腦缺血動物模式，以水迷宮實驗評估茶葉水粗抽物及其活性成分()-epigallocatechin gallate 對腦缺血大鼠學習操作障礙之改善作用，再輔以自發性運動量實驗評估其對自發性運動量之影響；並進一步測定其皮質區、海馬回及紋狀體之malonyldialdehyde 含量、superoxide dismutase 活性及total-glutathione 含量，以探討其抗氧化損傷；同時以pentoxifylline 為正對照藥物。 本研究首先探討茶葉水粗抽物及其活性成分()-epigallocatechin gallate 對改善腦缺血大鼠學習操作障礙之影響，由實驗結果顯示：大鼠前中腦動脈及兩側頸總動脈結紮所造成之腦缺血模式，可誘發大鼠於水迷宮空間操作、參考記憶、工作記憶再學習與再現等學習操作能力之障礙，茶葉水粗抽物及()-epigallocatechin gallate可改善因腦缺血所誘發之學習操作障礙。而正對照藥物pentoxifylline 雖亦有改善腦缺血所誘發之學習記憶障礙，但效果則不彰。 其次，本研究再探討茶葉活性成分()-epigallocatechin gallate 對學習記憶與抗氧化損傷之機制，由實驗結果顯示：腦缺血後大鼠海馬回及紋狀體區malonyldialdehyde 含量增加，而皮質區及海馬回中total-glutathione 的含量減少。()-epigallocatechin gallate可使腦缺血後大鼠海馬回及紋狀體malonyldialdehyde 含量降低及total-glutathione 含量增加，但正對照藥物pentoxifylline 對腦缺血後大鼠之malonyldialdehyde 含量增加及total-glutathione 的含量減少之現象，並無任何影響。 綜上所述，腦缺血誘發大鼠神經細胞損傷，會造成皮質區及海馬回中total-glutathione 的含量減少，進而造成腦部神經細胞氧化損傷而促使海馬回及紋狀體脂質過氧化的產物malonyldialdehyde 大量產生，而促使神經細胞損傷，進一步造成水迷宮空間操作、參考記憶、工作記憶再學習與再現等學習操作能力之障礙。茶葉水粗抽物可改善水迷宮空間操作、參考記憶、工作記憶再現等學習操作能力之障礙。茶葉主要活性成分()-epigallocatechin gallate 亦可改善水迷宮學習操作及記憶能力障礙，其作用機轉可能與減少海馬回及紋狀體之superoxide dismutase 活性，及增加total-glutathione 的含量，進而增加自由基之清除，減少malonyldialdehyde 的含量，降低腦缺血誘發神經細胞損傷。總之茶葉及其主要活性成分()-epigallocatechin gallate 改善腦缺血所誘發學習記憶障礙之作用機制與pentoxifylline 廻異。; Abstract The present study was designed to investigate the effects of Theae Folium (Camellia sinensis (L.) O. KUNTZE) and its principle constituent ()-epigallocatechin gallate on performance impairment of water maze and locomotor activity in cerebral ischemic rats caused by middle cerebral artery and two common carotid arteries occlusion. Then we further clarified the action mechanism of the ameliorating effects of ()-epigallocatechin gallate by measuring malonyldialdehyde and glutathione levels, and superoxide dismutase activity in rat cortex, hippocampus and striatum. Pentoxifylline was used as a positive control. Firstly, cerebral ischemic rats had the impairment of water maze spatial performance, and the deficits in reference and working memory. Theae Folium and its principle constituent ()-epigallocatechin gallate ameliorated the performance impairment and memory deficit in cerebral ischemic rats. Pentoxifylline also ameliorated the performance impairment induced by cerebral ischemia. Secondly, cerebral ischemic rats had higher malonyldialdehyde levels in hippocampus and striatum, and lower glutathione levels in cortex and hippocampus. ()-Epigallocatechin gallate reversed the deterioration of the malonyldialdehyde and glutathione levels in hippocampus and striatum. Pentoxifylline did not affect the deterioration of antioxidant defense and lipid peroxidation in cerebral ischemic rats. From these above results, cerebral ischemia caused oxidative damage of hippocampal and striatal nerve cells including glutathione depletion and malonyldialdehyde production, and then impaired spatial performance and memory processes in rats. Theae Folium ameliorated the memory impairment induced by cerebral ischemia. Its active constituent ()-Epigallocatechin gallate also ameliorated the memory impairment induced by cerebral ischemia, and the action mechanism might be due to decrease higher malonyldialdehyde levels via reversing the deterioration of total-SOD activity and glutathione levels in hippocampus and striatum. In summary, the action mechanism of the ameliorating effects of Theae Folium and its principle constituent ()-epigallocatechin gallate on the memory impairment induced by cerebral ischemia might is distinct from pentoxifylline.
