中药脑还丹对APP/PS1小鼠海马区细胞内[Ca^(2+)]i的影响

Effect of Naohuandan Granules on[Ca^(2+)]i in the Hippocampus Cell of APP/PS1 Double Transgenic Mice

目的观察中药脑还丹对APP/PS1双转基因小鼠学习记忆功能及海马区细胞内钙离子浓度([Ca^(2+)]i)的影响。方法将3个月龄APP/PS1双转基因小鼠(雄性)48只,随机分为模型组、脑还丹低剂量组、脑还丹高剂量组和多奈哌齐组,各12只,选取同月龄同遗传背景C57BL/6J小鼠12只为正常对照组。治疗组分别以脑还丹低剂量、高剂量浓缩液及多奈哌齐灌胃;正常对照组和模型组以同体积双蒸水灌胃,4个月后进行行为学测试,并测定各组小鼠海马组织细胞[Ca^(2+)]i。结果 Morris水迷宫实验结果 :与模型组比较,脑还丹高剂量组和多奈哌齐组逃避潜伏期较模型组明显缩短(P<0.01);与脑还丹低剂量组比较,脑还丹高剂量组和多奈哌齐组找到平台所用时间明显缩短(P<0.05)。与脑还丹低剂量组比较,高剂量组小鼠在定位航行中所用时间较少,平台象限内停留时间较长(P<0.05)。海马区[Ca^(2+)]i:5组小鼠海马区神经细胞内[Ca^(2+)]i比较,差异有统计学意义(P<0.05);与其他4组比较,模型组细胞内[Ca^(2+)]i明显增加(P<0.01);与脑还丹低剂量组比较,脑还丹高剂量组[Ca^(2+)]i水平较低(P<0.05)。结论脑还丹对APP/PS1双转基因小鼠学习记忆功能具有改善作用,这可能与其稳定海马区细胞内[Ca^(2+)]i,减少自由基产生,保护细胞生物膜,延缓神经元老化有关。

Objective To observe the Effect of Naohuandan granules on [ Ca^2＋] i in the hippocampus cell of APP/PS1 double transgen -ic mice.Methods Forty eight 3 months old male APP/PS1 double transgenic mice were randomLy divided into 4 groups,namely modelgroup（MG）,Naohuandan granules low dose group（NGL）,high dose group （NGH） and donepezil group（DG）,and anther 12 six monthsold C57BL/6J mice were recruited as a normal control group.The NGL and NGH were respectively given low and high dose Naohuan -dan granules orally,and the DG were perfused with donepezil（DP） solution,meanwhile,the model group and normal control group weregiven intragastric administration of double distilled water.Four months later,we observed the behavior of mice by Morris water mazetest.And 6 mice of each group were broken their neck to sacrifice after the water maze experiment,the whole brain were stripped outand the hippocampus tissue were isolated. The [ Ca^2＋] i of hippocampus was determined with flow cytometry.Results Comparedwith the model group,escape latency of APP/PS1 double transgenic mice in NGH and DG were significantly reduced （P 〈0.05）.How -ever,the time of staying in the original platform quadrant was obviously increased（P 〈0.05）.The results of the hippocampus [ Ca^2＋] ishowed that the hippocampus [ Ca^2＋] i of the model group was markedly increased compared with the normal control group and thetreated groups.Conclusion NG could improve the learning and memory ability of APP/PS1 double transgenic mice, the possiblemechanism might be through stabilizing the hippocampus [ Ca^2＋] i,slowing down the cell ′s aging process,and restoring the structureand function of synapses.