松果菊苷对阿尔采末病大鼠海马、皮质内神经递质水平的影响

Effect of echinacoside on monoamine neurotransmitters in hippocampus and cortex of rats with Alzheimer's disease

目的研究松果菊苷(ECH)对阿尔采末病(AD)模型大鼠海马、大脑皮质细胞外液中单胺类神经递质水平的影响,为ECH改善学习记忆力提供理论依据。方法 60只SD大鼠随机分为模型组、ECH低、中、高剂量组、阳性药石杉碱甲组以及假手术组。采用腹腔内注射D-半乳糖,并在右侧海马内注射Aβ25-35复制AD模型。Morris水迷宫评价各组大鼠学习记忆能力,应用脑双位点双通道同步微透析采样技术,联合运用高效液相-电化学法测定大鼠海马和皮质细胞外液中NA、DA、5-HT的含量。结果水迷宫结果显示,与假手术组相比,AD模型组大鼠逃避潜伏期明显延长(P<0.05),停留在原平台象限时间明显缩短(P<0.05);与模型组相比,ECH低、中、高剂量组均使大鼠学习记忆能力有不同程度的提高,ECH组逃避潜伏期明显缩短(P<0.05),停留在原平台象限时间明显延长(P<0.05)。同时,模型组较假手术组大脑皮质、海马中的NA、DA、5-HT明显降低(P<0.05);ECH组较模型组脑内单胺类神经递质水平恢复至接近正常水平。结论 ECH可以改善AD大鼠学习记忆力,并且明显升高海马、皮质细胞外液中单胺类神经递质的含量,具有一定的抗AD作用。并且ECH中、高剂量组、阳性药石杉碱甲组在提高学习记忆能力方面作用优于ECH低剂量组。

Aim To investigate the influence of echi-nacoside （ ECH ） on monoaminergic neurotransmitter extracellular of the hippocampus and cerebral cortex in rat model of Alzheimer′s disease （ AD） , and ultimately to provide a theoretical basis for ECH′s improving the ability of learning and memory. Methods 60 male SD rats were randomly divided into 6 groups with 10 rats in each group ： sham operation group, model, ECH groups of low, medium and high doses （10, 20, 40μg ＆#183;g-1 ＆#183;d-1 ） , and Hup A （ Huperzine A, 0. 02 μg＆#183; g-1＆#183;d-1） group. The AD rat model was established by abdominal cavity injection with D-galactose and uni-laterally injected with amyloid beta-protein fragment 25-35 （ Aβ25-35 ） into the right hippocampus. Morris wa-ter maze test was used to study the animals′ ability of spatial learning and memory. The synchronous dual-probe dual-channel brain microdialysis sampling tech-nology was applied to collect dialysates from different encephalic areas continuously, and combined with HPLC electrochemical detection were used to measure the extracellular levels of norepinephrine （ NE） , dopa-mine （DA）, 5-serotonin （5-HT）. Results 1. Com-pared with the sham operation group, the mean escape latency of the model group was significantly prolonged （ P〈0. 05 ） , and the time that rats were in the plat-form quadrant was significantly shortened （ P〈0. 05 ）;on the contrary, compared with the model group, the mean escape latency of ECH groups were significantly shortened （ P〈0. 05 ） , and the time that rats were in the platform quadrant was significantly extended （ P〈0. 05）. 2. Compared with the sham operation group, the contents of NE,DA and 5-HT were significantly de-creased in the model group （ P 〈0. 05 ） . However, compared with the model group , ECH could improve＆amp;nbsp;the concentrations of NE, DA, 5-HT in the hippocam-pus and cerebral cortex, and these monoamine levels of the brain regions were restored to near control. Con-clusion ECH can effectively improve the ability of learning and memory of rats with AD, giving a rise to the monoamine neurotransmitter both in hippocampus and cortex, exerting a positive effect on treatment of cognitive dysfunction . The ECH low dose group is sig-nificantly lower than the ECH groups of medium and high doses and Hup A group in improving the ability of learning and memory.