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目的应用D-半乳糖(D-galactose)及Aβ25-35联合建立阿尔茨海默病(Alzheimer’s Disease,AD)大鼠模型。采用脑立体定位技术、脑微透析技术及高效液相-荧光检测技术等研究松果菊苷(ECH)对阿尔茨海默病模型大鼠海马细胞外液中兴奋性氨基酸递质含量的影响,以探讨其对脑保护作用的可能机制。方法将50只雄性Wistar大鼠随机分为对照组和造模组,对照组10只,造模组40只。给造模组大鼠腹腔注射D-半乳糖(100 mg·kg-1),每天1次,共计腹腔注射42d。第43天用微量进样针在大鼠海马部位注射5μl Aβ25-35。对照组注射等量生理盐水。造模结束后通过Morris水迷宫检测筛选出具有行为学异常(潜伏期延长)的大鼠,将其随机分为模型组、ECH大剂量组、ECH小剂量组和石杉碱甲组,连续给药14 d,每日一次。于第14天进行大鼠海马微透析试验,将微透析液注入高效液相-荧光检测系统,测定各组海马细胞外液中兴奋性氨基酸谷氨酸和天门冬氨酸的含量。结果与模型组相比,ECH大剂量组、ECH小剂量组和石杉碱甲组海马透析液中兴奋性氨基酸的含量降低,具有统计学意义。结论应用D-半乳糖及Aβ25-35联合建立阿尔茨海默病大鼠模型的方法可行,ECH能对抗AD大鼠海马细胞外液中兴奋性氨基酸的毒性作用,可用于AD的防治。
Objective To establish a rat model of Alzheimer’s Disease (AD) by using D-galactose and Aβ25-35. The effects of echinacoside (ECH) on the content of excitatory amino acid neurotransmitters in the hippocampal extracellular fluid of Alzheimer’s disease model rats were studied by stereotaxic technique, brain microdialysis technique and high performance liquid chromatography-fluorescence detection technique. To explore its possible mechanism of brain protection. Methods Fifty male Wistar rats were randomly divided into control group and model group, control group (n = 10) and model group (n = 40). Rats in model group were intraperitoneally injected with D-galactose (100 mg · kg-1) once a day for a total of 42 days. On day 43, 5 μl of Aβ25-35 was injected into the hippocampus of the rat using a micropipette. The control group was injected with normal saline. After modeling, rats with behavioral abnormalities (prolonged latency) were screened by Morris water maze test and randomly divided into model group, high dose ECH group, low dose ECH group and huperzine A group 14 d, once daily On the 14th day, rat hippocampal microdialysis test was performed. The microdialysate was injected into the high performance liquid-fluorescence detection system to determine the excitatory amino acids glutamic acid and aspartic acid in the hippocampus of each group. Results Compared with the model group, the content of excitatory amino acids in the ECH high dose group, ECH low dose group and huperzine A hippocampus dialysate decreased significantly, with statistical significance. Conclusion The method of combining D-galactose with Aβ25-35 to establish a rat model of Alzheimer’s disease is feasible. ECH can antagonize the toxic effect of excitatory amino acids in the extracellular fluid of hippocampus of AD rats and can be used for the prevention and treatment of AD.