乌灵菌粉对APPswe/PS1dE9阿尔兹海默病模型小鼠认知功能、Aβ1-42和p-Tau蛋白的影响

Effect of Wu-Ling Powder therapy on cognition, Aβ1-42 and p-Tau expression in APPswe/PS1dE9 double transgenic AD mice

目的探讨分析乌灵菌粉对APPswe/PS1dE9双转基因阿尔兹海默病模型小鼠认知功能、Aβ1-42和p-Tau的影响。方法 APPswe/PS1dE9双转基因小鼠20只,随机分成2组,每组10只,雌雄各半,即疾病模型组、乌灵菌粉组[剂量为100 mg/(kg·d)];C57BL/6品系的正常小鼠10只作为健康对照组,雌雄各半。乌灵菌粉组灌胃给药共30 d,疾病模型组和健康对照组同期给予相同体积生理盐水代替,正常喂食。3组小鼠先后进行Morris水迷宫实验、定位航行实验和空间搜索实验。在末次给药1 h后,脱颈椎处死各组小鼠,采用酶联免疫吸附方法(ELISA)检测3组Aβ1-42、p-Tau蛋白在小鼠海马中的含量。结果①与健康对照组比较,乌灵菌粉组在逃避潜伏期、目标象限游泳时间、有效区停留时间和经过平台次数均显著增加(均P<0.01);与疾病模型组比较,乌灵菌粉组在逃避潜伏期、目标象限游泳时间、有效区停留时间和经过平台次数均显著下降(均P<0.05)。②与健康对照组比较,乌灵菌粉组小鼠海马中的Aβ1-42含量和p-Tau蛋白均显著增加(均P<0.01);与疾病模型组比较,乌灵菌粉组小鼠海马中的Aβ1-42含量显著降低(P<0.01)。结论乌灵菌粉能够改善APPswe/PS1dE9双转基因阿尔兹海默病模型小鼠记忆和学习能力,可能是通过减少小鼠海马中Aβ1-42含量来影响Aβ聚集体的形成,从而减少老年斑的生成。

Objective To explore the effect of Wu-Ling Powde therapy on cognition, Aβ1-42 and p-Tau expression in APPswe/PS1dE9 double transgenic AD mice. Methods Twenty APPswe/PS1dE9 double transgenic AD mice, half male and half female, were randomly divided into disease model group, Wu-Ling Powder group [at the dosage of 100 mg/(kg·d)]. Additionally,10 normal C57 BL/6 mice(half male and half female) were used as the healthy control group. The disease model group and the healthy control group were given the same volume of normal distilled water,and the Wu-Ling Powder group was administrated by gavage for 30 days, respectively. All animals were fed normally.The behavioral tests such as Morris water maze test, place navigation test and probe trial testing were carried out in these groups. All the mice in three groups were killed in one hour after the last medication,hippocampus of these mice were separated for the detection of Aβ1-42 and p-Tau by enzyme-linked immunosorbent assay(ELISA). Results ① Compared with the healthy control group, the latent period of the Wu-Ling Powder group in water maze test, target quadrant swimming time, effective zone residence time and platform times were increased significantly(all P<0.01);compared with the disease model group, the latent period in water maze test, target quadrant swimming time, effective zone residence time and platform times of the Wu-Ling Powder group were decreased significantly(all P<0.01).② Compared with the healthy control group, the expression levels Aβ1-42 and p-Tau in hippocampus of the Wu-Ling Powder group were increased significantly(all P<0.01);compared with the disease model group, the expression levels Aβ1-42 in hippocampus of the Wu-Ling Powder group were decreased significantly(P<0.01). Conclusion Wu-Ling Powder has an effect on improving learning and memory ability, it may reduce the formation of Aβaggregates by decreasing the content of Aβ1-42 in the hippocampus of mice, and thus reducing the generation of senile plaques.