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作 者:欧阳石[1] 孙莉莎[1] 郭胜蓝[1] 刘旭[1] 徐江平[1]
机构地区:[1]南方医科大学药理教研室,广东广州510515
出 处:《第一军医大学学报》2005年第2期121-126,共6页Journal of First Military Medical University
基 金:SupportedbyNational863ProgramofChinaforNewDrugResearchandDevelopment(2003AA2Z3535)andNaturalScienceFoundationofGuangdongProvince(2KB04207S)
摘 要:目的建立大鼠β-淀粉样肽[Aβ(25-35)]诱导的痴呆模型,探讨知母总皂苷在阿耳茨海默病(AD)发病机制中的作用。方法SD大鼠60只,采用脑立体定位技术在大鼠单侧侧脑室一次性注射老化的Aβ(25-35)建立实验性AD模型。手术24h后,大鼠经灌胃分别给予3种剂量的知母总皂苷和EGB761,模型组和空白组给予等剂量的蒸馏水,1次/1d,连续14d。在给予Aβ(25-35)后的第8天,应用Morris水迷宫法测定大鼠的学习记忆功能,造模后第14天断头取脑,测定脑组织超氧化物歧化酶(SOD)、丙二醛(MDA)和总抗氧化能力。结果与空白对照组相比,模型组大鼠空间学习记忆能力明显减弱,寻找平台潜伏期明显延长(P<0.01);脑组织SOD、总抗氧化能力明显降低(P<0.01),而MDA明显升高(P<0.05)。与模型组比较,给予知母总皂苷治疗后的大鼠学习记忆功能障碍得到明显改善,潜伏期显著缩短(P<0.05),SOD活力显著提高(P<0.05),总抗氧化能力也显著增强(P<0.05),MDA水平明显降低(P<0.05)。结论知母总皂苷可明显改善AD模型大鼠的学习记忆功能,同时可提高模型大鼠的抗过氧化能力,这有可能是其改善学习记忆的原因之一。Objective To investigate the effects of timosaponins, one group of the two major components of Anemarrhean asphodeloides Bge, on the learning and memory capacities of rats with dementia induced by amyloid β-peptide (25-35) [Aβ (25-35)]. Methods Sixty SD rats were randomized into 6 groups (n=10) and except for those in the control group, all other rats were subjected to lateral cerebral ventriclar injection of aggregated Aβ (25-35) to prepare rat models of dementia. Twenty- four hours after the injection, the rats received intragastric administration of timosaponins at 3 different doses (treatment group) or Ginkgo biloba extract EGB761 on a daily basis for 14 consecutive days. From postoperative days 8 to 14 after Aβ (25-35) injection, Morris water maze test was performed to evaluate the effects of Aβ (25-35) and the therapeutic agents timosaponins on the learning and memory capacity of the rats. On day 14, the level of malonaldehyde (MDA), superoxide dismutase (SOD) activity and total antioxidation capacity in the brain tissue of the rats were measured. Results Aβ (25-35) induced significant learning and memory impairment in the rats, which had lowered SOD activity and total antioxidation capacity (P<0.01) with elevated MDA level (P<0.05). Compared with the rats in dementia model group, those receiving timosaponin treatment at different doses all manifested alleviation of learning and memory impairment (P<0.05), with enhanced SOD activity (P<0.05) and total antioxidation capacity (P<0.01) and reduced MDA level (P<0.05) in the brain tissue. Conclusion Timosaponins can remarkably enhance the learning and memory capacities in rats with Aβ (25-35)-induced dementia, presumably in relation to their actions to promote the scavenging of the free radicals.
关 键 词:知母总皂苷 beta样淀粉蛋白 Morris水迷宫测试 痴呆 自由基
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