表没食子儿茶素没食子酸酯对APP/PS1双转基因小鼠神经元突触可塑性和神经细胞黏附分子表达的影响

目的 观察表没食子儿茶素没食子酸酯 (EGCG) 对淀粉样前体蛋白（APP）/早老素1(PS1)双转基因小鼠空间学习记忆能力、海马 CA1 区突触超微结构和神经细胞黏附分子表达的影响。方法 选用 8 周龄雄性APP/PS1双转基因小鼠随机分为模型组、EGCG组、盐酸多奈哌齐组，另以同窝阴性小鼠设立正常组，每组 12 只。连续灌胃给药 6 个月后进行相关指标检测。采用 Morris 水迷宫实验观测APP/PS1转基因小鼠空间学习记忆能力；透射电子显微镜观察小鼠海马CA1区突触超微结构; 分别采用免疫荧光法及免疫印迹法检测APP/PS1转基因小鼠海马CA1区神经细胞黏附分子（NCAM）和唾液酸转移酶（ST8Sia Ⅱ）的蛋白表达。结果 与正常组比较，模型组逃避潜伏期延长；与模型组比较，EGCG组、盐酸多奈哌齐组小鼠逃避潜伏期下降 (P＜0.05)。电子显微镜结果显示，与模型组比较，EGCG组和盐酸多奈哌齐组突触界面曲率变化不明显；突触间隙宽度变窄，突触后致密物厚度增加（P＜0.05）。免疫荧光结果显示，海马CA1区NCAM、ST8Sia Ⅱ蛋白表达在神经元的胞体内，EGCG组和盐酸多奈哌齐组NCAM、ST8Sia Ⅱ蛋白表达明显增加 (P＜0.05)，免疫印迹实验发现其含量亦呈高表达水平(P＜0.05)。结论 EGCG对 APP/PS1 转基因小鼠的空间学习记忆功能具有改善作用，其机制可能与影响小鼠海马突触结构，提高小鼠海马神经黏附分子表达有关。

Effect of epigallocatechin gallate on expressions of synaptic plasticity and neural cell adhesion molecules in APP/PS1 double transgenic mice

Objective To observe the effect of epigallocatechin gallate (EGCG) on the spatial learning memory deficit in amyloid procursor protein(APP)/presenilin-1(PS1) double transgenic mice, synaptic ultrastructure and expression of neural cell adhesion molecule in hippocampal CA1 region.Methods Eight weeks old male APP/PS1 double transgenic mice were selected as Alzheimer’s disease (AD) model and divided into the model group, the EGCG group and the donepezil hydrochloride group, 12 in each group.Besides，normal mice of the same brood (with no transgene) were recruited as a normal group (n=12). Related indices were detected after 6 months continuous gastrogavage. The spatial learning-memory deficit of APP/PS1 double transgenic mice was detected by Morris water maze test.The synaptic ultrastructure of hippocampal CA1 region was observed by transmission electron microscopy. The expression levels of neural cell adhesion molecule (NCAM) and polysialyltranseferase α2,8-polysialic acid (ST8Sia Ⅱ) protein in hippocampal CA1 region of APP/PS1 transgenic mice were detected by immunofluorescence and Western blotting.Results Compared with the normal group, the mean value of escape latency in the model group was extended, and compared with the model group, the mean value of escape latency in the EGCG group and donepezil hydrochloride group were increased (P<0.05). The result of electron microscope showed that the changes of synaptic interface curvature of EGCG group and donepezil hydrochloride group were not obvious. Compared with the model group, the width of the synaptic gap becomes narrower and the thickness of the post synaptic compact were increases (P<0.05). Immunofluorescence showed that the expression of NCAM and ST8Sia Ⅱ proteins in the hippocampus CA1 region was expressed in the cytoplasm of neurons, the expressions of NCAM and ST8Sia Ⅱ in hippocampal CA1 region were significantly increased in EGCG group and donepezil hydrochloride group (P<0.05). Their contents also showed higher levels of expression in Western blotting (P<0.05).Conclusion EGCG shows improvement on the spatial learning memory deficit in APP/PS1 double transgenic mice，which may be associated with affecting the synaptic structure of hippocampus and improving the expressions of neural cell adhesion molecule.