臺灣博碩士論文加值系統

之前研究指出銀杏葉萃取物(EGb761)在動物模式及病人急性中風時具有多種益處。本研究目的為探討餵食銀杏葉萃取物(EGb761, 100mg/kg/day )合併抗缺血藥物MK801或FK506之療法對沙鼠短暫局部腦缺血梗塞體積之協同作用。實驗一分為對照組及EGb761組，餵食實驗飼料7天後，將沙鼠右側之中腦動脈(middle cerebral artery, MCA)及總頸動脈(common carotid artery, CCA)結紮，缺血一小時後，進行再灌流，抗缺血藥物MK801在缺血前，FK506 則在缺血前或後30分鐘腹腔給藥(1 mg/kg)，24±1小時後犧牲取全腦，在腦切盒中冠切，厚度為2mm，進行2 % 2, 3, 5-triphenyltetrazolium chloride (TTC)染色，之後利用自動影像分析系統計算腦梗塞體積%。在實驗一結果中發現，(a)餵食EGb761的各組其梗塞體積比例明顯較對照組低；(b)餵食EGb761的各組間：缺血前加上MK801治療與EGb761組效果沒有差異，缺血後給予FK506，其腦梗塞體積比例較EGb761組低；又FK506在缺血後給予其梗塞體積比例有較缺血前低的趨勢，因此設計第二個實驗。實驗二餵食實驗飼料14天，於缺血後30分鐘給予FK506 (1mg/kg)，實驗流程與實驗一相同。實驗二的結果發現，餵食EGb761及在缺血後給予FK506其腦梗塞體積比例在14天的數值較7天佳( p<0.05)。因此，餵食銀杏葉萃取物(EGb761)合併抗缺血藥物之療法可減少沙鼠短暫局部腦缺血梗塞體積。

Previous studies indicated that Ginkgo biloba extract (EGb761) provides beneficial effects in animal model and patients during acute stroke. The purpose of this study was to investigate the synergistic effect of EGb761 combined with anti-ischemia drugs MK801 & FK506 to infarct volume % of gerbil in a transient focal cerebral ischemia. Experiment 1: the animals were divided into two groups : control and EGb761 group, fed standard chow or EGb761(100 mg/kg/day) for 7 days, then induced ischemia by ligating right middle cerebral artery (MCA) and common carotid artery (CCA) for one hour, then reperfusion. The subgroup combined with anti-ischemia drugs MK801 (1mg/kg) was administered intraperitoneally before 30-min of ischemia, with FK506 administered intraperitoneally before or after 30-min of ischemia. Sacrifice was performed after 24±1 hours. The brain was immediately removed, cut into 2mm coronal sections using a brain matrix, and stained according to the standard 2 % 2, 3, 5-triphenyltetrazolium chloride (TTC) method. Infarct volume % was measured by automated image analyzer. In experiment 1, results suggested that (a) the subgroups of the EGb761 group, the infarct volume % was significantly lower than control; (b) between the subgroups of the EGb761 group: the infarct volume % of MK801 treatment before ischemia was not significantly different from that of EGb761 group; the infarct volume % of gerbils given FK506 after ischemia was significantly lower than EGb761 group; but the infarct volume % appears to be lower when FK506 was given after ischemia. Thus, we designed experiment 2. Experiment 2 fed the gerbils EGb761 (100 mg/kg/day) for 14 days the protocal was the same with experiment 1 with FK506 being administered intraperitoneally after 30-min of ischemia. In experiment 2, results showed that the infarct volume % of gerbils which fed with EGb761 for 14 days combined with FK506 were better than those fed for 7 days (p<0.05), but there were no significantly difference between the two group. The results suggest that gerbils fed with EGb761 combined with anti-ischemia drugs can decrease infarct volume % of gerbil in a transient focal cerebral ischemia.

中文摘要…………………………………………………………I
英文摘要………………………………………………………..III
目錄……………………………………………………….……..V
表目錄…………………………………………………….….VIII
圖目錄………………………………………………………….IX
第一章 前言………………………………………………...1
第二章 文獻回顧……………………………………..…….3
第一節 腦中風……………………………………………..3
壹、腦中風的流行病學…………………………………3
貳、腦中風的種類………………………………………4
叁、腦中風的危險因素…………………………………7
肆、腦中風的預防與治療……………………………..13
第二節 銀杏的簡介………………………………………15
壹、銀杏的介紹………………………………………..15
貳、EGb761的介紹……………………………………16
叁、EGb761的化學結構………………………………17
肆、EGb761與腦中風相關研究………………………21
第三節 FK506…………………………………………….29
壹、FK506簡介………………………………………..29
貳、FK506的化學結構………………………………..31
叁、FK506與腦中風相關研究………………………...32
第四節 MK801…………………………………………….34
壹、MK801簡介………………………………………..34
貳、MK801的化學結構………………………………..35
叁、MK801與腦中風相關研究………………………..36
第三章 材料與方法………………………………………..38
第一節 實驗動物……………………………………………38
壹、實驗動物……………………………………………38
貳、動物分組……………………………………………39
叁、動物結紮及再灌流之模式…………………………44
肆、腦部梗塞體積之測量……………………………….45
第二節 實驗飼料…………………………….…………….. 48
第四章 結果與討論……………………………………..…51
第一節 實驗一結果與討論…………………………………51
壹、體重及飼料攝取量……………………………….. .51
貳、梗塞體積比例及梗塞面積………………………….51
第二節 實驗二結果與討論………………………………....57
壹、體重及飼料攝取量…………………………………..57
貳、梗塞體積比例及梗塞面積…………………………..57
第五章 結論………………………………………………..66
第六章 參考文獻…………………………………………..67

表目錄
頁次
表一 常見急性腦血管病鑑別表…………………………………….6
表二 福壽公司實驗動物飼料組成份…………………………........49
表三 實驗飼料組成............................................................................50
表四 沙鼠餵食7天含EGb761飼料後體重與攝食量之變化…….54
表五 沙鼠餵食14天含EGb761飼料後體重與攝食量之變化.......60

圖目錄
頁次
圖一 山奈黃素( kaemferol)之化學結構……………………..17
圖二 槲皮酮(quercetin)之化學結構........................................18
圖三 楊梅素(myricetin)之化學結構........................................18
圖四 銀杏內酯(ginkgolide)的化學結構..................................19
圖五 白果內酯的化學結構......................................................20
圖六 細胞內鈣離子增加使神經鈣蛋白磷酸化之訊號過程..30
圖七 FK506 (tacrolimus)的化學結構.......................................31
圖八 MK801(dizocilpine)((+)-5-methyl-10,11-dihydro-
5H-dibenzo﹝a,d﹞cyclohepten-5, 10-imine maleate)
的化學結構………………………………………….......35
圖九 實驗一之實驗設計...........................................................40
圖十 實驗一之實驗流程...........................................................41
圖十一 實驗二之實驗設計...........................................................42
圖十二 實驗二之實驗流程……………………………………...43
圖十三 腦部背部及側面構造圖...................................................47
圖十四 實驗一中不同治療組別之梗塞體積比例.......................55
圖十五 實驗一中各組間不同部位之梗塞面積………………...56
圖十六 實驗二中不同治療組別之梗塞體積比例……………...61
圖十七 實驗二中各組間不同部位之梗塞面積………………...62

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