基于GluR1探讨益肾化浊方对快速老化模型小鼠学习记忆能力及神经元突触效能的影响  

Exploration of Effect of Yishen Huazhuo Decoction(益肾化浊方)on Learning and Memory Ability and Neuronal Synaptic Efficiency of SAMP8 Mice Based on GluR1

作　　者：覃启京 张玉莲[2] 于臻[3] 张伟[3] 张琳琳[2] QIN Qijing;ZHANG Yulian;YU Zhen;ZHANG Wei;ZHANG Linlin(Guangxi International Zhuang Medicine Hospital,Nanning 530201,China;The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300250,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]广西国际壮医医院脑病科,南宁530201 [2]天津中医药大学第二附属医院,天津300250 [3]天津中医药大学,天津301617

出　　处：《山东中医杂志》2020年第6期596-602,共7页Shandong Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(编号:81873272);天津市卫生和计划生育委员会中医中西医结合科研课题(编号:2017135)。

摘　　要：目的:观察益肾化浊方对快速老化模型小鼠(SAMP8小鼠)学习记忆能力、神经元突触效能和突触AMPA受体亚基GluR1含量的影响,探讨益肾化浊方治疗阿尔茨海默病的作用机制。方法:将40只7月龄SAMP8小鼠随机分为模型组和益肾化浊方组,每组各20只,同时选取同月龄抵抗快速老化小鼠(SAMR1小鼠)20只作为对照组。益肾化浊方组小鼠每日按6.24 g/kg的剂量予益肾化浊方水煎液灌胃1次,对照组和模型组小鼠每日给予等量蒸馏水灌胃1次。各组小鼠连续灌胃4周后,通过Morris水迷宫实验检测学习记忆能力,利用透射电子显微镜观察小鼠海马CA1区神经元和突触超微结构变化,并用激光共聚焦显微镜观察小鼠海马突触后膜上GluR1的含量。结果:Morris水迷宫实验显示,与对照组比较,模型组小鼠逃避潜伏期明显延长、穿越平台次数明显减少,差异有统计学意义(P<0.05);与模型组比较,益肾化浊方组小鼠逃避潜伏期明显缩短、穿越平台次数明显增加,差异有统计学意义(P<0.05)。透射电子显微镜观察发现,与模型组比较,益肾化浊方组小鼠神经元细胞核呈椭圆形,核膜尚清晰完整,染色质细腻,核仁明显,细胞器病变改善;突触前膜、后膜结构尚清晰可见,突触间隙明显。激光共聚焦显微镜观察发现,对照组小鼠海马神经元突触后膜的GluR1含量丰富,模型组含量极少,益肾化浊方组含量较模型组增加。结论:益肾化浊方可通过促进AMPA受体亚基GluR1的表达,调控神经元细胞“胞吐-内化”过程,有效保护神经元和突触超微结构的完整性,改善SAMP8小鼠突触传递效能,进而改善其学习记忆能力。Objective:To observe the effect of Yishen Huazhuo Decoction(益肾化浊方)on learn-ing and memory ability,neuronal synaptic efficiency and GluR1 content of synaptic AMPA receptor subunit of senescence accelerated mice prone/8(SAMP8),so as to explore the mechanism of Yishen Huazhuo Decoction in treatment of AD.Methods:A total of 407-month SAMP8 were randomly divided into model group and Yishen Huazhuo Decoction(YSHZD)group,with 20 mice in each group.At the same time,207-month senescence accelerated mice-resistance/1(SAMR1)mice were selected as the control group.The mice in the YSHZD group were given the decoction by gavage at a dose of 6.24 g/kg,once a day for 4 weeks,while the mice in the control group and the model group were given equal volume of distilled water by gavage,once a day for 4 weeks.After the gavage,morris water maze test was employed to evaluate the learning and memory ability of the mice.Ultrastructural changes of neurons and synapses in the CA1 region of the mice’s hippocampus were observed by transmission electron microscopy.The content of GluR1 in the postsynaptic membranes of the mice’s hippocampus was observed by confocal laser scanning microscopy.Results:The water maze test showed that compared with the the control group,the escape latency of the mice in the model group was significantly increased(P<0.05),and the number of crossing platform of the mice in the model group was significantly reduced(P<0.05).Compared with the model group,the escape latency of the mice in the YSHZD group was significantly reduced(P<0.05),and the number of crossing platform of the mice in the YSHZD group was significantly increased(P<0.05).Observed by the transmission electron microscope,the nucleus of the neurons of the mice in the YSHZD group was oval,with clear and complete nuclear membrane,delicate chromatin,obvious nucleoli and alleviated lesions of the organelles,and the presynaptic membrane and postsynaptic membrane structure were still clearly visible with obvious synaptic cleft,which was better than

关 键 词：益肾化浊方 阿尔茨海默病 快速老化模型小鼠 学习记忆能力 GLUR1 胞吐-内化 突触效能 

分 类 号：R285.5[医药卫生—中药学]