臺灣博碩士論文加值系統

中文摘要
已有很多報導顯示Sigma-1作用劑有抗失憶的作用尤其是改善p-chloroamphetamine ( 5-HT釋放劑)，dizocilpine ( glutamate NMDA 接受器離子通道的阻斷劑)或scopolamine (乙醯膽鹼接受器拮抗劑)等引致之失憶。因此，我們使用ICR小鼠腦部細胞膜樣品建立sigma- 1接受器結合性試驗來評估十二種中藥水抽提物是否對sigma-1接受器有相互作用。結果發現十二種中藥水抽提物皆對sigma-1接受器有親和力，其親和力大小範圍從黃連之Ki=1.85x10-3 mg/ml至柴胡之Ki= 5.21 mg/ml。以適用ICR小鼠之方形水迷宮置放學習模式來評估這些中藥是否也都具有抗失憶的效果，結果發現大棗(1.5-3.0 g/kg, i.p.)、香附(3.5-5.0 g/kg, i.p.)、石菖蒲(0.5-1.5 g/kg, i.p.)在scopolamine (8.0 mg/kg, i.p.)前10分鐘預處理與只給scopolamine比較，在記憶測試時會減少游到平台區域的時間並且會增加停留在平台區域的時間，即具有抗失憶作用。為了檢驗這些中藥之抗失憶作用是否與sigma-1接受器活化有關，我們使用sigma-1拮抗劑haloperidol (0.25 mg/kg, i.p.)與這些中藥同時注射來評估。結果顯示haloperidol可以逆轉sigma-1作用劑SKF-10047 (3.0 mg/kg, i.p.)所產生的抗失憶作用但卻對大棗、香附、石菖蒲所產生的抗失憶作用，沒有明顯的影響。因此可知大棗、香附、石菖蒲的抗失憶作用並非經由sigma-1接受器媒介。相對地，於所測試中藥中對於sigma-1接受器具有最高親和力之黃連，在0.1 mg/kg下可以逆轉由SKF-10047所產生的抗失憶作用，所以黃連具有像sigma-1拮抗劑的作用。

英文摘要
Many studies have shown that sigma-1 receptor agonists exert potent antiamnesic effects by improving learning and memory impairments induced by p-chloroamphetamine (a 5-HT releaser), dizocilpine (a glutamate NMDA receptor channel blocker), or scopolamine (a muscarinic acetylcholine receptor antagonist). To evaluate whether the water extracts from 12 Chinese herbal drugs can interact with the sigma-1 receptors, a sigma-1 receptor binding assay using mice brain membrane preparations was established and used. The results indicated that these water extracts all interacted with the sigma-1 receptors with different affinities ranging from Huanglian (Ki=1.85x10-3 mg/ml) to Chaihu (Ki=5.21 mg/ml). To evaluate whether they have antiamnesic effects, this study used placing learning in a rectangular water maze adapted for mice. As compared with scopolamine alone, Dazao (1.5-3.0 g/kg, i.p.), Xiangfu (3.5-5.0 g/kg, i.p.), or Shichangpu (0.5-1.5 g/kg, i.p.) administrating 10 min before scopolamine (8.0 mg/kg, i.p.) increased the latency to reach the platform location and decreased the time spent within the platform location at the retention test session. To test whether an activation of sigma-1 receptors is involved in their antiamnesic effects, a sigma-1 receptor antagonist haloperidol (0.25 mg/kg, i.p.) was co-administered with the test Chinese drug. Haloperidol was able to reverse the antiamnesic effect of a sigma-1 receptor agonist SKF-10047 (3.0 mg/kg, i.p.) but had no significant effect on Dazao, Xiangfu, or Shichangpu. Therefore, these results indicated that the antiamnesic effects of Dazao, Xiangfu, and Shichangpu are not via sigma-1 receptors. In contrast, Huanglian (0.1 mg/kg, i.p.), having the highest affinity for the sigma-1 receptor among the test Chinese herbal drugs, was able to reverse the antiamnesic effect of SKF-10047. Therefore, Huanglian acts like a sigma-1 receptor antagoinist.

目錄
中文摘要
英文摘要
緒 論…………………………………………………………………1
研究目的…………………………………………………………………7
實驗材料及方法………………………………………………………..16
一.實驗動物與藥品試劑之來源………………………………...16
1.動物………………………………………………………..16
2.實驗藥品與試劑…………………………………………..16
3.中藥的來源與水抽提物備…………………………….….17
二.實驗方法……………………………………………………...17
1.接受器結合驗………………………………………….….17
2.水迷宮之空間記憶實驗…………………………………..20
三. 統計方法……………………………………………………...21
實驗結果………………………………………………………………..22
一. Sigma-1接受器結合性實驗………………………………….22
二. 水迷宮測試之建立…………………………………………...22
三. 中藥水抽取物之抗失憶作用………………………………...24
1.柴 胡……………………………………………………....24
2.香 附………………………………………………………24
3.大 棗………………………………………………………25
4.木 通………………………………………………………26
5.遠 志………………………………………………………26
6.黃 連………………………………………………………27
7.徐長卿……………………………………………………..28
8.單 參………………………………………………………28
9.玄 參………………………………………………………29
10.地骨皮……………………………………………………..29
11.蛇床子……………………………………………………..30
12.石菖蒲……………………………………………………..31
四. Haloperidol之拮抗……………..…………………………….31
五. 黃連對SKF-10047之拮抗……..…………………………….32
六. Berberine對SKF-10047之拮抗……………………………32
討 論………………………………………………………………..33
參考文獻………………………………………………………………..41
圖 表………………………………………………………………..51

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