连翘酯苷对拟AD复合动物模型小鼠学习记忆的改善作用及其机制研究

目的以β淀粉样蛋白损伤自然衰老小鼠建立一种新的复合式老年痴呆(AD)小鼠模型,观察连翘酯苷对复合模型学习记忆障碍的改善作用,并对其机制进行初步探讨。方法采用14月龄C57BL/6小鼠侧脑室注射Aβ25-35形成拟AD复合模型;Morris水迷宫实验观察小鼠学习记忆能力,实验结束取小鼠脑组织用放射免疫分析法检测TNF-α及IL-1的含量;Western blot方法检测GFAP蛋白表达,化学比色法测定ChAT、AchE、SOD酶活性及MDA的含量。结果水迷宫实验中连翘酯苷组可显著改善小鼠的学习记忆能力(P<0.05)。作用机制研究发现:连翘酯苷能降低TNF-α、IL-1的含量(P<0.05),抑制GFAP蛋白表达。提高ChAT、SOD酶活力,降低AchE活性及MDA的含量(P<0.05,P<0.01)。结论连翘酯苷对拟AD复合动物模型学习记忆的改善作用可能与抑制脑内炎症反应,调节胆碱能系统,抗氧化作用等有关。

Nootropic effect of forsythiaside on a novel complex mouse model of Alzheimer disease and its mechanism

Objective To establish a novel complex mouse model of Alzheimer disease（AD） induced by β-amyloid protein in aged mice and to investigate the nootropic effect of forsythiaside on the disease.Methods 14 months old C57BL/6 mice were injected β-amyloid 25-35（Aβ25-35） into lateral ventricles to establish a mouse model of Alzheimer disease.Morris water maze test was used to evaluate the mouse learning and memory function.The concentrations of interleukin-1β（IL-1β） and tumor necrosis factor-α（TNF-α） in the hippocampus were determined by radioimmunoassay.Glial fibrillary acidic protein（GFAP） in hippocampal astrocytes was determined by Western blot electrophoresis.Acetylcholine esterase（AchE）,choline acetyltransferase（ChAT）,superoxide dismutase（SOD） activity and oxidation products malondialdehyde（MDA） content were assayed by chemical colorimetry.Results Forsythiaside improved the learning and memory capacity of AD model mice significantly.Forsythiaside significantly decreased the concentrations of IL-1β and TNF-α in the hippocampus and inhibited the expression of GFAP in AD model mice.Forsythiaside improved the activity of SOD and ChAT,decreased the activity of AchE and inhibited the formation of MDA.Conclusions The nootropic effect of forsythiaside on β-amyloid-induced complex mice model of Alzheimer disease may be related with the inhibition of inflammation,adjustment of central cholinergic nerve transmitter activity and antioxidative effect.