地黄饮子对APP/PS1小鼠工作记忆及海马超微结构影响的研究  

Effect of Dihuang Yinzi on Working Memory and Hippocampus Ultrastructure of APP/PS1 Mice

作　　者：李全[1] 张健 王琪 周妍妍[2] LI Quan;ZHANG Jian;WANG Qi;ZHOU Yanyan(The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150040, China;Heilongjiang University of Chinese Medicine, Harbin 150040, China)

机构地区：[1]黑龙江中医药大学附属第一医院,黑龙江哈尔滨150040 [2]黑龙江中医药大学基础医学院,黑龙江哈尔滨150040

出　　处：《中医药学报》2022年第4期28-32,共5页Acta Chinese Medicine and Pharmacology

基　　金：国家自然科学基金项目(81774197,81803984);黑龙江省博士后科研基金项目(LBH-Z20193);黑龙江中医药大学研究生创新科研项目(2020yjscx012)。

摘　　要：目的:探讨地黄饮子对APP/PS1双转基因痴呆小鼠工作记忆及海马超微结构的影响。方法:将6月龄APP/PS1小鼠随机分为实验第1、2、3个月地黄组(D1、D2、D3)、模型组(M1、M2、M3),同月龄同背景阴性小鼠作为空白组(B1、B2、B3)。通过Y迷宫测试不同实验月份的各组小鼠工作记忆能力,通过透射电镜观察不同实验月份的各组小鼠海马CA1区超微结构。结果:实验各月份小鼠进臂总次数无差异(P>0.05);实验第1个月的M1组与B1组小鼠相比自发交替率显著降低(P<0.01),D1组与M1组小鼠相比自发交替率显著提高(P<0.05);实验第2、3个月的M2组与B2组相比、M3组与B3组相比小鼠自发交替率均显著降低(P<0.01),D2组与M2组相比、D3组与M3组相比小鼠自发交替率均显著提高(P<0.01);此外,M3组与M2、M1组相比小鼠自发交替率显著降低(P<0.05,P<0.01)。透射电镜观察发现,实验各月份的空白组小鼠海马CA1区神经细胞无明显改变,模型组小鼠海马CA1区神经细胞逐渐发生凋亡改变,线粒体肿胀变形,并伴有脂褐素和溶酶体存在,经地黄饮子干预后的D1、D2组小鼠海马CA1区线粒体轻度肿胀,并且D3组小鼠海马CA1区神经细胞形态结构已与空白组相接近。结论:APP/PS1小鼠随着月龄增加工作记忆能力呈进行性下降,线粒体发生肿胀变形,并且至小鼠9月龄时出现大量的凋亡小体;地黄饮子可改善APP/PS1小鼠随月龄增长而下降的工作记忆能力,并抑制神经细胞凋亡,改善线粒体形态结构。Objective:To investigate the effects of Dihuang Yinzi on working memory and hippocampus ultrastructure in mice with APP/PS1 double transgene dementia.Methods:APP/PS1 mice of 6 months were randomly divided into the Dihuang groups of one month,two months and three months(D1,D2,D3)and the model group(M1,M2,M3),the mice with same months old and same background were assigned into the blank control groups(B1,B2,B3).The memory capabilities of the mice with different months were detected through Y maze testing,and the hippocampus ultrastructure of CA1 region was observed in mice of different months by transmitting electron microscopy.Results:There was no statistical difference in the total number of arm entering among the mice of difference months(P>0.05).In terms of the spontaneous alternation rate,it was significantly lower in M1 group than that in B1 group(P<0.01);it was significantly higher in D1 group than that in M1 group(P<0.05);it was significantly lower in M2 group and M3 group than that in B2 group and B3 group(P<0.01);it was significantly higher in D2 group and D3 group than that in M2 group and M3 group(P<0.01);in addition,it was significantly lower in M3 group than that in M2 group and M1 group(P<0.05,P<0.01).Transmission electron microscope observation showed that there was no obvious change in the neurons of hippocampal CA1 area in the blank groups.In the model groups,the neurons of hippocampal CA1 area were gradually apoptotic,and the mitochondria were swollen and deformed,accompanied by lipofuscin and lysosome.After the intervention of Dihuang Yinzi,the mitochondria of hippocampal CA1 area became less swollen in D1 group and D2 group,morphological structure of neurons in hippocampal CA1 area in D3 group was similar to that in B3 group.Conclusion:With the increase of age,the working memory ability of APP/PS1 mice decreased progressively,the mitochondria swelled and deformed,and a large number of apoptotic bodies appeared at the age of 9 months.Dihuang Yinzi can improve the working memory ability of APP/PS

关 键 词：阿尔茨海默病 地黄饮子 工作记忆 海马超微结构 

分 类 号：R285.5[医药卫生—中药学]