活血开窍方改善APP/PS1双转基因AD模型小鼠学习记忆能力的机制研究

Study on the mechanism of Huoxue Kaiqiao Formula to improve learning and memory ability of APP/PS1 double transgenic AD mice

目的:研究活血开窍方对APP/PS1双转基因AD模型小鼠海马CA1区AchE、ChAT、Aβ、APP表达的影响,探讨其改善该模型小鼠学习记忆能力的作用机制。方法:3月龄APP/PS1双转基因AD小鼠,随机分为活血开窍大剂量组、活血开窍小剂量组、盐酸多奈哌齐组、模型组,C57BL/6J小鼠为正常组,每组10只,连续灌胃给药3个月,Morris水迷宫观测小鼠学习记忆能力的变化,免疫组化法检测小鼠海马CA1区AchE、ChAT、Aβ、APP表达。结果:Morris水迷宫结果表明,与正常组比较,模型组小鼠穿越原平台位置的次数、第四象限游泳时间及游泳路程均显著性缩短和减少(P<0.01);与模型组比较,活血开窍组上述3个指标均显著性提高(P<0.05,P<0.01)。小鼠海马CA1区AchE、Aβ、APP阳性细胞个数、阳性细胞面积比例显著性减少(P<0.05,P<0.01),ChAT阳性细胞个数显著性增多(P<0.05,P<0.01)。结论:活血开窍方可改善APP/PS1双转基因AD模型小鼠学习记忆能力,其机制与降低小鼠海马CA1区AchE、Aβ、APP表达,提高胆碱能系统ChAT表达有关。

Objective:To study the effects of Huoxue Kalqiao Formula on the expression of AchE,CHAT,A β and APP in hippocampal CA1 region of APP/PS1 double transgenic AD model mice,and to explore its mechanism of improving the learning and memory ability of mice in this model.Methods:Three-month-old APP/PS1 double transgenic AD mice were randomly divided into a large dose group of Huoxue Kaiqiao,a small dose group of Huoxue Kaiqiao,a donepezil hydrochloride group,a model group,and C57BL/6J mice as a normal control group,with 10 rats in each group.The rats were administered with continuous gavage for 3 months.Morris water maze was used to observe the changes of learning and memory ability of mice.The expression of AchE,CHAT,A β and APP in hippocampal CA1 area was detected by immunohistochemistry.Results:Morris water maze results showed that compared with the normal control group,the number of mice crossing the original platform position and the swimming time and distance of the fourth quadrant in the model group were significantly shortened and reduced (P<0.01). After the intervention,compared with the model group,the number of times of swimming through the original platform and the swimming time and distance of the fourth quadrant in the Morris water maze in the Huoxue Kalqiao group were significantly increased (P<0.05,P<0.01).The number of AchE,A β and APP positive cells and the proportion of positive cell area in the hippocampal CA1region of the mice was significantly decreased (P<0.05,P<0.01),and the number of ChAT positive cells was significantly increased (P<0.05,P<0.01).Conclusion:Huoxue Kaiqiao Formula can improve the learning and memory ability of APP/PS1double transgenic AD model mice.The mechanism is related to reducing the expression of AchE,A β and APP in hippocampal CA1 region,increasing ChAT expression in cholinergic system and decreasing AchE expression.