柚皮苷及其与吴茱萸碱联合用药对APP^(swe)/PS^(ΔE9)转基因痴呆模型小鼠学习记忆能力的影响

Effects of naringin and its combination with evodiamine on learning and memory in APP^(swe)/PS^(ΔE9) transgenic mice

目的探讨柚皮苷及柚皮苷与吴茱萸碱联合用药对APPswe/PSΔE9转基因痴呆模型小鼠学习记忆能力的影响,研究柚皮苷与吴茱萸碱联合使用是否具有协同或叠加作用。方法 APPswe/PSΔE9转基因痴呆模型小鼠随机分组,每组12只,雌雄各半,分别选择在3月龄和5月龄两个时间段开始进行治疗,各给药组按设定剂量分别单独或联合加入鼠粮中。3月龄给药16周、5月龄给药4周后进行水迷宫实验,以安理申作为阳性药对照,并与安慰剂组小鼠进行比较。Thioflavin-S荧光染色检测单独使用柚皮苷治疗转基因小鼠脑组织老年斑的形成。结果单独使用柚皮苷4周和16周,缩短寻找平台的潜伏期分别为22%、32%;单独使用吴茱萸碱4周和16周,缩短寻找平台的潜伏期分别为33%、10%。柚皮苷治疗16周减少海马老年斑26%。柚皮苷与吴茱萸碱联合应用能够显著缩短寻找平台的潜伏期47%。结论单独使用柚皮苷或吴茱萸碱均能改善痴呆模型小鼠的学习记忆能力,柚皮苷长期的使用优于短期的治疗效果,但是吴茱萸碱短期有效,长期作用反而下降;柚皮苷与吴茱萸碱联合应用能够显著改善APPswe/PSΔE9痴呆模型小鼠的学习记忆能力,但联合用药组并未表现出强于单独给药组的协同保护效应。

Objective To investigate the effects of naringin and the combined application of naringin with evodiamine on cognitive ability in APPswe/PSΔE9 transgenic mice,and to compare the difference of neuroprotective effects between the applications of these two drugs alone or in combination,and to determine whether there is synergistic or additive effect of the combination of naringin and evodiamine.Methods ① APPswe/PSΔE9 transgenic mice aged 3 months and 5 months were randomly divided into different groups,12 in each group.The mice performed Morris water maze test after administration of the drugs for 4 weeks and 16 weeks,respectively.The drugs were mixed in the diet singly or in combination according to the grouping protocol.One group was used as vehicle group and one group was used as Aricept group.The littermates receiving placebo were used as normal control.②The senile plaques were detected by Thioflavin-S staining and visualized directly by fluorescence microscopy.Results ① Compared with the APPswe/PSΔE9 transgenic mice,naringin administrated alone for 4 weeks and 16 weeks showed a significantly decreased latency by 22% and 32%,respectively;and evodiamine administrated alone for 4 weeks and 16 weeks showed a decreased latency by 33% and 10%,respectively.② The senile plaques were decreased by 26% in the hippocampus of mice after 16 weeks naringin administration.③ The combined application of naringin with evodiamine showed the decreased latency by 47%,compared with the APPswe/PSΔE9 transgenic mice,however,when compared with naringin alone,the combined application showed no more decreased latency.Conclusions Either naringin or evodiamine can improve the cognitive deficits in APPswe/PSΔE9 transgenic mice.Long-term effect of naringin is obviously better than its short-term effect.However,on the contrary,short-time use of evodiamine is effective but its long-time effect is decreased.The combined application of naringin with evodiamine can obviously improve the cognitive ability in APPswe/PSΔE9 transgenic mice,however,it shows no synergetic protective effect compared with the use of naring in alone.