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作 者:赵婷婷[1,2] 张全斌[2] 张忠山[2] 王晶[2] 李智恩[2] 徐祖洪[2]
机构地区:[1]中日友好医院临床医学研究所药物药理室,北京100029 [2]中国科学院海洋研究所,山东青岛266071
出 处:《中药新药与临床药理》2010年第2期160-163,共4页Traditional Chinese Drug Research and Clinical Pharmacology
基 金:山东省优秀中青年科学家奖励基金(2007BS07004)
摘 要:目的观察褐藻多糖硫酸酯(FPS)对β-淀粉样肽(1-40)(Aβ1-40)右侧脑室注射诱导的阿尔茨海默病(Alzheimer's disease,AD)小鼠认知障碍的作用及机制。方法小鼠右侧脑室注射凝聚态Aβ1-403ng,制作AD模型。实验分为FPS低、中、高剂量治疗组(50,100,200mg·kg-·1d-)1、阳性药盐酸多奈哌齐组(2.5mg·kg-·1d-)1、模型组和假手术组,于造模后24h分别灌胃给药16d。术后第11天开始进行避暗试验和水迷宫试验,分别检测小鼠的学习和记忆能力,试验结束后测定皮层、海马组织胆碱乙酰转移酶(ChAT)和乙酰胆碱酯酶(AchE)活力变化。结果与假手术组相比,模型组小鼠的学习、记忆能力显著下降,脑内ChAT活力和AchE活力显著变化;与模型组对比,低、中、高剂量FPS显著改善AD小鼠空间学习记忆能力,增加皮层和海马内ChAT活力,抑制AchE活力。结论FPS有改善Aβ1-40诱导的AD模型小鼠空间学习记忆障碍的作用,其机制与升高脑内乙酰胆碱含量有关。Objective To study the effect of fucoidan on the learning and memory impairment m Alzhelmer's disease fAD)model mice induced by aggregated β-amyloid peptide (1-40)(Aβ31-40). Methods AD mice model was estab- lished by injected Aβ31-40 into the right mice ventricle. The model mice were administered with fucoidan (50, 100, 200 mg·kg-1· d-1, ig), Donepezil (2.5mg·kg-1· d-1, ig) and daily ig injections of normal saline for 16 days respec- tively 24 hours after aggregated Aβ intracerebroventricular injection. The cognitive ability of AD model was detected by water amaze test and passive avoidance test from the 1 lth day. Then the animals were sacrificed and the activity of acetylcholinesterase(AChE)and choline acetyltransferase(CHAT)in the conical and hippocampal tissue were examined by colorimetric method. Results The ability of learning and memory was significant lowered, and the activities of cerebral CHAT and AChE changed in AD group as compared with the sham-operation group. Fucoidan (50, 100, 200 mg·kg-1· d-1, ig) significantly ameliorated the learning and memory impairment induced by Aβ1-40. Biochemical analy- sis showed that fucoidan increased CHAT activity and decreased AChE activity in the conical and hippocampal tissue. Conclusion Fucoidan can significantly improve the learning and memory impairment in mice with AD induced by Aβ1-40, and the mechanism may be related with the increase of cerebral acetylcholine content.
关 键 词:褐藻多糖硫酸酯 学习记忆障碍 β-淀粉样肽(1-40) 阿尔茨海默病
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