牛膝改善大鼠學習記憶障礙之研究

The Study of Achyranthes Bidentata on Learning and Memory Impairment in Rats

10.6516/TJTCM.201809_21(2).0001

吳龍源(Lung-Yuan WU)；呂峻安(Chun-An Lu)；吳啟瑞(Chi-Rei Wu)；蔡汎修(Fan-Shiu Tsai)；蔡金川(Chin-Chuan Tsai)；林立偉(Li-wei Lin)

類澱粉樣蛋白 ； 阿茲海默症 ； 水迷宮 ； 牛膝 ； amyloid β peptide ； Alzheimer's disease ； water maze ； Actyranthes bidentate

中醫藥研究論叢

21卷2期（2018 / 09 / 30）

1 - 8

繁體中文

背景：阿茲海默症主要臨床症狀為記憶能力喪失，其病理特徵為老年斑，而老年斑主因類澱粉樣蛋白（amyloid β-peptide）沉積所致，基於此理論本實驗設計應用amyloid β peptide（Aβ_(1-40)）來誘發阿茲海默症學習障礙之動物模型，並以水迷宮來評估中藥牛膝改善學習記憶障礙的作用。材料&方法：本計畫以80% 乙醇及水進行藥材萃取及分離，分別提取純化而製得懷牛膝皂苷提取物（ABS）及懷牛膝多醣體提取物（ABP）；後進行對Aβ_(1-40)誘導大鼠記憶障礙改善作用之評估。結果：Aβ_(1-40)可造成大鼠於水迷宮之操作障礙暨短期記憶與參考記憶之障礙。ABS於50 mg/kg可改善Aβ_(1-40)側腦室輸注所導致水迷宮空間操作暨參考記憶能力之障礙；而ABP於100 mg/kg也能改善Aβ_(1-40)側腦室輸注所導致水迷宮空間操作暨參考記憶能力之障礙。結論：懷牛膝之成分ABS及ABP能改善Aβ_(1-40)誘導大鼠水迷宮學習記憶障礙，可供中醫藥臨床基礎研究參考。

Purpose: Alzheimer's disease (AD) is characterized by neuropathological hallmarks such as senileplaque and neurofibrillary tangles caused by the amyloid β peptide (Aβ_(1-40)). For this reason, we demonstratedthe role of the improve effect of Achyranthesbidentata against continuous intracisternal injection of Aβ_(1-40) in rats. Materials & Methods: This present result obtained total saponins and total polysaccharides extracted from Actyranthes bidentate (ABS and ABP) by 80% ethanol and distilled water. We further investigated the effects of ABS and ABP on the memory function caused by Aβ_(1-40) in rats. Intracisternal injection of Aβ_(1-40) caused the dysfunction of memory function on water maze. Results: Pretreatment with ABS at a dosage of 50 mg/kg or ABP at 100 mg/ kg reversed the dysfunction of memory function on water maze caused by intracisternal injection of Aβ_(1-40). Conclusions: ABS and ABP can improve the learning and memory impairment of rat water maze induced by Aβ_(1-40), which can be used as a reference for clinical basic research of traditional Chinese medicine.

1. https://www.moi.gov.tw/chi/chi_news/news_detail.aspx?type_code=02&sn=13723
2. Abraham, C.R.(1989).Alpha 1-antichymotrypsin is present together with the beta-protein in monkey brain amyloid deposits.Neuroscience,32(3),715-20.
3. Clark, R.E.,Broadbent, N.J.,Squire, L.R.(2007).The hippocampus and spatial memory: findings with a novel modification of the water maze.J Neurosci,27(25),6647-54.
4. Del Olmo, N.(2006).Hippocampal synaptic plasticity and water maze learning in cocaine self-administered rats.Ann N Y Acad Sci,1074,427-437.
5. Galani, R.(1998).Spatial memory, habituation, and reactions to spatial and nonspatial changes in rats with selective lesions of the hippocampus, the entorhinal cortex or the subiculum.Behavioural Brain Research,96(1-2),1-12.
6. Griffith, H. R.,Netson, K. L.,Harrell, L. E.,Zamrini, E. Y.,Brockington, J. C.,Marson, D. C.(2006).Amnestic mild cognitive impairment: diagnostic outcomes and clinical prediction over a two-year time period.J Int Neuropsychol Soc,12,166-75.
7. Harkany, T.(1999).N-methyl-D-aspartate receptor antagonist MK-801 and radical scavengers protect cholinergic nucleus basalis neurons against beta-amyloid neurotoxicity.Neurobiology of Disease,6(2),109-121.
8. Lin, Y.C.(2003).The ameliorating effects of cognition-enhancing Chinese herbs on scopolamine- and MK-801-induced amnesia in rats.Am J Chin Med,31(4),543-9.
9. Morris, R.G.,Salmon, D.P.(2007).The centennial of Alzheimer's disease and the publication of "Uber eine eigenartige Erkankung der Hirnrinde" by Alois Alzheimer.Cortex,43(7),821-5.
10. Nagahara, A.H.,McGaugh, J.L.(1992).Muscimol infused into the medial septal area impairs long-term memory but not short-term memory in inhibitory avoidance, water maze place learning and rewarded alternation tasks.Brain Res,591(1),54-61.
11. Porte, Y.,Buhot, M.C.,Mons, N.E.(2008).Spatial memory in the Morris water maze and activation of cyclic AMP response element-binding (CREB) protein within the mouse hippocampus.Learn Mem,15(12),885-94.
12. Su, J.(2010).Curcuma comosa improves learning and memory function on ovariectomized rats in a long-term Morris water maze test.J Ethnopharmacol,130(1),70-5.
13. Zajaczkowski, W.(1997).Uncompetitive NMDA receptor antagonists attenuate NMDA-induced impairment of passive avoidance learning and LTP.Neuropharmacology,36(7),961-71.
14. Zhang, C.(2010).Familial Alzheimer's disease mutations in presenilin 1 do not alter levels of the secreted amyloidbeta protein precursor generated by betasecretase cleavage.Curr Alzheimer Res,7(1),21-6.
15. 袁秀榮、常章富(2002)。懷牛膝、川牛膝本草考證。中國中藥雜誌，27(7)，545。
16. 馬愛蓮、郭煥(1998)。懷牛膝抗衰老作用研究。中藥材，21(7)，360-362。
17. 陳紅、劉友平(2001)。川牛膝多糖抗腫瘤作用初探。成都中醫藥大學學報，24(1)，49-50。
18. 趙中振(2006)。當代藥用植物典。