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 establish a rat model of dementia induced by β-amyloid peptide [Aβ(25-35)] and investigate the role of total timosaponins in the pathogenesis of Alzheimer’s disease (AD). Methods Sixty Sprague-Dawley rats were used to establish an experimental model of AD by injecting aged Aβ(25-35) into the unilateral lateral ventricle of rats by stereotactic technique. Twenty-four hours after the operation, rats were given 3 doses of timosaponin and EGB761 by gavage. The model and blank groups were given equal doses of distilled water once a day for 1d for 14 days. On the 8th day after administration of Aβ(25-35), the learning and memory function of rats was measured by Morris water maze test. The brain was decapitated on the 14th day after the model was established to determine the superoxide dismutase (SOD) in the brain. Malondialdehyde (MDA) and total antioxidant capacity. Results Compared with the blank control group, the spatial learning and memory ability of the model group rats was significantly weakened, the latent period of the search platform was significantly prolonged (P<0.01), and the SOD and total antioxidant capacity of the brain tissue were significantly reduced (P<0.01), while the MDA significantly increased. High (P<0.05). Compared with the model group, learning and memory dysfunction after treatment with total saponins from anemarrhenas was significantly improved, latency was significantly shortened (P<0.05), SOD activity was significantly increased (P<0.05), and total antioxidant capacity was also significantly increased ( P<0.05), MDA levels decreased significantly (P<0.05). Conclusion Anemarrhena total saponins can significantly improve the learning and memory function of rats with AD, and at the same time can improve the anti-peroxidation ability of model rats, which may be one of the reasons for improving learning and memory.