地黃及其成分梓醇對大鼠改善學習記憶障礙作用之研究; The attenuating effects of Rehmanniae Radix and catalpol

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Title:	地黃及其成分梓醇對大鼠改善學習記憶障礙作用之研究;The attenuating effects of Rehmanniae Radix and catalpol
Authors:	林穎志;Ying-Chih Lin
Contributors:	中國醫藥學院中國藥學研究所
Keywords:	被動迴避學習反應;主動迴避學習反應;腦缺血;水迷宮
Date:	1992
Issue Date:	2009-12-22 10:32:14 (UTC+8)
Abstract:	摘要智力增進劑對於各種動物學習記憶障礙模式均具增強或改善作用，包括水迷宮、被動迴避學習反應、主動迴避反應等。本研究即以上述模式探討地黃及其成分梓醇對智力增進作用之評估。並探討地黃及其成分梓醇改善雙側頸動脈結紮腦缺血、類澱粉樣蛋白連續輸注大鼠之學習記憶障礙，與腦中單胺濃度的關係。結果顯示地黃甲醇粗抽物於30-300 mg/kg可增強低刺激之被動迴避學習障礙，而於300 mg/kg能延長因SCOP誘發大鼠之明室滯留時間縮短現象，亦能延長因腦缺血誘導大鼠之明室滯留時間縮短現象，及改善腦缺血大鼠水迷宮學習操作、參考記憶與工作記憶障礙。其正丁醇層粗抽物於10-30mg/kg下可增強低刺激之被動迴避學習障礙，延長因SCOP誘發大鼠之明室滯留時間縮短現象及腦缺血大鼠之明室滯留時間縮短現象，並改善SCOP與腦缺血誘導大鼠水迷宮學習操作、參考記憶與工作記憶障礙，但水層粗抽物則無明顯改善效果。梓醇(10 µg/kg)能延長大鼠因SCOP誘發、腦缺血、類澱粉樣蛋白連續輸注等所造成之明室滯留時間縮短現象，對SCOP、腦缺血大鼠水迷宮學習操作、參考記憶與工作記憶障礙亦具改善之作用，梓醇(10 µg/kg)可改善因類澱粉樣蛋白連續輸注大鼠誘發之主動迴避障礙與水迷宮學習操作、參考記憶障礙。接著探討梓醇改善學習記憶與中樞神經系統之關係，結果顯示梓醇(10 ?g/brain, i.c.v.)不能改善縫核注射中樞血清毒素5,7-DHT(25 µg/brain)、海馬迴注射中樞腎上腺β拮抗劑PROP (80 ng/brain)、海馬迴注射中樞腎上腺α2 拮抗劑 YOH (80 ng/brain)誘導水迷宮學習操作障礙;然而梓醇(10 ?g/brain i.c.v.)可以明顯改善海馬迴注射中樞乙醯膽鹼神經毒素AF64A (3 ?g /brain)、藍斑核注射中樞catecholamine神經毒素6-OHDA (25 ?g/brain)、海馬迴注射中樞cholinergic拮抗劑SCOP (3.2 ng /brain)、海馬迴注射中樞腎上腺α1 拮抗劑 PHEN (80 ng/brain)誘導之水迷宮學習操作障礙。在腦缺血大鼠與類澱粉樣蛋白連續輸注大鼠兩者之海馬迴之DA, DOPAC與皮質之DA濃度有升高的現象，而梓醇有明顯減少DA, DOPAC濃度上升之作用，並有明顯提升NE濃度之作用。綜合上述結果，梓醇能降低大腦海馬迴與皮質DA之濃度、及提升NE濃度，其改善學習記憶之作用與中樞兒茶酚胺神經系統、中樞膽鹼神經系統、腎上腺α1接受體有關，但與中樞之血清胺神經系統無關。; ABSTRACT Cognition-enhancing drugs could facilitate the performance in some kinds of animal learning and memory deficit models, including water maze, pass and active avoidance learning performances. We evaluated the cognition-enhancing effect of Rehmanniae Radix and catapol, an active constituent of Rehmanniae Radix, by using these animal models. Furthermore, we measured monoamine levels in the cortex and hippocampus of the cerebral ischemic rats and Aβ4- treated rats to demonstrate the attenuating mechanisms of Rehmanniae Radix and its constituent catalpol on the cerebral ischemia and Aβ4- induced learning and memory deficits. The results showed that the methanolic extract of Rehmanniae Radix (RM) at the dose of 30-300 mg/kg facilitated the inhibitory avoidance response with a low stimulus in rats. Moreover, 300 mg/kg RM reversed the step-through latency (STL) shortened by scopolamine or cerebral ischemic rats. It also shortened the swimming time reaching to the hidden platform on Morris water maze spatial performance and working memory, and enhanced the swimming time spent in the target ring on reference memory in cerebral ischemic rats. The butanolic (10-30mg/kg) but not water layer of methanolic extract of Rehmanniae Radix facilitated the inhibitory avoidance response with a low stimulus. In addition, it reversed the STL shortened by scopolamine and cerebral ischemic rats, shortened the swimming time reaching to the hidden platform on Morris water maze spatial performance and working memory, and enhanced the swimming time spent in the target ring on reference memory in scopolamine-treated rats and cerebral ischemic rats. Catalpol (10 µg/kg), the major constituent of Rehmanniae Radix reversed the STL shortened by scopolamine, cerebral ischemic rats and Aβ4- infused rats and shortened the swimming time reaching to the hidden platform on Morris water maze spatial performance and working memory. It also enhanced the swimming time spent in the target ring on reference memory in scopolamine-treated rats and cerebral ischemic rats. Catalpol (10 mg/kg s.c.) also facilitated the spatial performance of Morris water maze but not working memory in Aβ4- infused rats and improved active avoidance learning performance deficit of cerebral ischemic rats and Aβ4- infused rats . Furthermore, we investigated the relationship between the ameliorating effect of catapol on the learning and memory and central neuronal systems. The results showed that catalpol at 10 ?g/brain (i.c.v.) did not ameliorate the performance impairment induced by 5, 7-DHT (25 µg/brain, intra-raphe), PROP (80 ng/brain, intrahippocampus), and YOH (80 ng/brain, intrahippocampus) on Morris water maze. However, catalpol at 10 ?g/brain (i.c.v) significantly improved
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