银杏内酯B对阿尔茨海默病大鼠海马Synapsin-1、Beclin1和LC3表达的影响

Effect of inkgolide B on the Expression of Synapsin-1,Beclin1 and LC3 in Hippocampus of Alzheimer's Disease Rats

目的:探讨银杏内酯B(ginkgolide B,GB)对阿尔茨海默病(alzheimer’s disease,AD)大鼠海马Synapsin-1、Beclin1和LC3的影响。方法:将大鼠按随机数字表法分为假手术组、模型组、银杏内酯B低剂量组、中剂量组和高剂量组,采用Morris水迷宫检测学习记忆,透射电镜观察自噬,免疫组织化学分析海马Synapsin-1、Beclin1和LC3阳性神经元光密度值,荧光定量PCR检测海马Synapsin-1、Beclin1和LC3-Ⅱ的mRNA水平。结果:中、高剂量银杏内酯B可缩短AD大鼠逃避潜伏期,增加穿越平台次数,减少自噬体,提高海马组织Synapsin-1,降低Beclin1 mRNA和蛋白表达,同时下调LC3-ⅡmRNA水平。结论:银杏内酯B可改善AD大鼠学习记忆能力,可能与海马突触相关蛋白Synapsin-1上调、自噬相关基因Beclin1和LC3水平下降有关。

Objectivel： To evaluate the efficiency of Ginkgobalide B （GB） on the expression of Synapsin-1, Beclinl and LC3 in the hippocampus of Alzheimer disease＇ s rats （AD rats）. Methods Rats were randomly divided into four groups： sham group, model group, three Ginkgobalide B groups of low dose, middle dose and high dose respectively. The Morris water maze （MWM） test was used to assess behaviors of the rats, Transmission electron microscope （ TEM ） was used to observe autophagy in hippocampal CA1 neurons of each group, Imunohistochemical staining was used to test Synapsin-1, Beclinl and LC3 in the hippocampal CA1, Real-time PCR was used to examine Synapsin-1, Beclinl and LC3-Ⅱ mRNA levels. Results ： MWM test result showed that escape latency was significantly shower and the times of crossing the platform increased. GB could promote hippocampal CA1 neurons autophagy. Imunohistochemical staining result displayed that Synapsin-1 increased and Beclinl decreased in the hippocampal CA1 after GB（5, 7.5mg/kg）treatment. Real-time PCR manifested that compared with the model group, Synapsin-1 increased, Beclinl and LC3-Ⅱ decreased in the hippocampus after GB（5, 7. 5mg/kg）treatment. Conclusion GB can improve learning and memory in AD rats, and its mechanism might be associated with Synapsin-1, Beclinl and LC3.