酸枣仁皂苷对Alzheimer病大鼠认知功能障碍改善的实验研究

Effect of Jujuboside on the Cognitive Dysfunction of Alzheimer Disease in Rats

目的:研究酸枣仁皂苷对Alzheimer病认知障碍的影响。方法:选用老年雄性SD大鼠36只,将大鼠随机分为正常组、模型组、给药组。采用D-半乳糖、Aβ1-42双因素复制AD大鼠模型。第6周采用Morris水迷宫检测认知功能,第7周末从大鼠的心脏处取血,离心取出血清,Elisa法检测血清大鼠血清褪黑素(MT)、褪黑素受体(MTR)、5-羟色胺(5-HT)的含量,免疫组化方法检测海马p-tau蛋白表达。结果:(1)Morris水迷宫定位航行实验中,模型组逃避潜伏时间长于用药组(P<0.05);在空间探索实验中,模型组大鼠每分钟穿越平台的次数少于用药组(P<0.05);(2)模型组大鼠血清5-HT、MT、MTR的浓度低于正常组(P<0.05),与模型组相比,用药组的5-HT、MT、MTR的浓度均上调(P<0.05);(3)模型组海马区Tau蛋白Ser199位点过磷酸化阳性表达细胞计数高于正常组(P<0.05),用药组的阳性细胞计数低于模型组(P<0.05)。结论:酸枣仁皂苷对AD大鼠认知记忆有改善作用,作用机制可能是通过提高5-HT、MT、MTR的浓度,延缓Tau蛋白过度磷酸化而达到的。

Objective： To observe jujuboside on the curative effect of cognitive impairment of Alzheimer disease. Methods： 36 old male SD rats were randomly divided into normal group,model group and administration group. AD rat model was induced by D-galactose and A beta 1-42. At the sixth week,using Morris water maze test of cognitive function,and the seventh week,blood was taken from the heart of rats,serum was the by centrifugalization,serum melatonin（ MT） and melatonin receptor（ MTR）,5-serotonin content（ 5-HT） were detected by Elisa method,the expression of hippocampal p-tau protein was detected though immunohistochemical method. Results：（ 1） In Morris water maze navigation experiment,rats of the model group escape latency time was longer than the administration group（P〈0. 05）; in the space exploration experiment,the number of rats per minute across the platform is less than the administration group（P〈0. 05）.（ 2） Compared with the normal group rats,serum level of 5-HT,MT,MTR in the model group rats were significantly decreased（P〈0. 05. Compared with the model group,Jujuboside might rise serum level of 5-HT,MT,MTR（P〈0. 05）.（ 3） The positive expression of Ser199 protein in the hippocampus,compare with the normal group,the positive cell count in the model group was increased（P〈0. 05）. By contrast,the positive cell count in the administration group was reduced（P〈0. 05）.Conclusion： Jujuboside had improved cognition and memory of AD rats. The mechanism may be through increased concentration of 5-HT,MT,MTR,delayed Tau protein hyperphosphorylation.