目的 观察电针百会、大椎、肾俞穴对SAMP8小鼠学习记忆与海马CA1区神经元突触的影响,探讨电针治疗阿尔茨海默病(AD)的机制。方法 7月龄SAMP8小鼠24只随机分为模型组和电针组,同龄正常老化SAMR1小鼠12只为对照组。电针组电针百会、大椎、肾俞穴30 d。Morris水迷宫检测小鼠学习记忆能力,免疫组织化学观察小鼠海马CA1区突触素(SYN)及突触后致密区蛋白95 (PSD95)的表达,透射电镜观察小鼠海马CA1区突触超微结构的变化。结果 与模型组相比,电针组逃避潜伏期缩短(P<0.05),原平台象限停留时间延长(P<0.05),穿越原平台次数增加(P<0.05),海马CA1区SYN与PSD95表达显著提高(P<0.001),突触结构较完整,数量增加。结论 电针能提高小鼠海马CA1区神经元突触蛋白的表达,改善突触的超微结构,从而有效改善SAMP8小鼠的学习记忆能力。
Objective To observe the effect of electroacupuncture (EA) at Baihui (GV20), Dazhui (GV14) and Shenshu (BL23) acupoints on cognitive function and the synapse of neurons in hippocampal CA1 in SAMP8 mice, to explore the mechanism of EA in the treatment of Alzheimer's disease (AD).Methods A total of 24 seven-month-old SAMP8 mice were randomly divided into model group (n=12) and EA group (n=12), and the same age SAMR1 mice were as control group (n=12). The EA group accepted EA at Baihui, Dazhui and Shenshu for 30 days. They were assessed with Morris maze test. The expression of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) in hippocampal CA1 region were detected with immunohistochemistry. The morphology and density of synapse in hippocampal CA1 region was observed with transmission electron microscopy.Results Compared with the model group, the latency of Morris maze decreased in EA group (P<0.05), the time staying in the quadrant of the platform increased (P<0.05), as well as the number passing the original platform (P<0.05), with the more expression of SYN and PSD95 in hippocampal CA1 region (P<0.001), and more and completed synapse.Conclusion EA can improve the learning and memory ability of SAMP8 mice by increasing the expression of SYN and PSD95 to protect the ultrastructure of synapses in hippocampal CA1 region.
[1] 周勇,王炎,刘丽娜. 哌罗匹隆与喹硫平治疗老年痴呆患者精神行为症状的对照研究[J]. 中国临床药理学与治疗学, 2013, 18(1): 90-94.
[2] Querfurth HW, La Ferla FM. Alzheimer's disease [J]. N Engl J Med, 2010, 362(4): 329-344.
[3] Sheng M, Sabatini BL, Sudhof TC. Synapses and Alzheimer's disease [J]. Cold Spring Harb Perspect Biol, 2012, 4(5): 747-749.
[4] Selkoe DJ. Alzheimer's disease is a synaptic failure [J]. Science, 2002, 298(5594): 789-791.
[5] Yuki D, Sugiura Y, Zaima N, et al. DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease [J]. Sci Rep, 2014, 4(4): 7130.
[6] Dong W, Guo W, Zheng X, et al. Electroacupuncture improves cognitive deficits associated with AMPK activation in SAMP8 mice [J]. Metab Brain Dis, 2015, 30(3): 777-784.
[7] 董卫国,林岚,王丰,等. 电针对SAMP8小鼠海马线粒体呼吸链功能的影响[J]. 中国针灸, 2012, 32(8): 726-730.
[8] 余曙光,郭义. 实验针灸学[M]. 北京:人民卫生出版社, 2012: 252.
[9] 罗磊,孙国杰,杜艳军,等. “益肾调督”针灸法对阿尔茨海默病大鼠海马神经元线粒体动力学相关蛋白的影响[J]. 针刺研究, 2015, 40(4): 270-274.
[10] 何勋,于杰,孙国杰,等. 益肾调督法针灸对阿尔茨海默病模型大鼠海马神经元线粒体融合蛋白的影响[J]. 中国预防医学杂志, 2014, 15(3): 187-190.
[11] 崔翔,马冉,唐萁,等. 益肾调督针灸法对AD大鼠海马线粒体CypD的影响[J]. 中华中医药杂志, 2014, 29(7): 2374-2376.
[12] 陈阳阳,孔立红,孙国杰,等. “益肾调督”针灸法对AD大鼠血清Aβ及海马APP表达的影响[J]. 时珍国医国药, 2016, 27(9): 2289-2291.
[13] 王丰,吕东,李长征,等. 电针对SAMP8小鼠海马Beclin-1表达的影响[J]. 山西医科大学学报, 2015, 46(8): 721-723.
[14] Tskeda T. Senescence-accelerated mouse (SAM) with special references to neurodegeneration models, SAMP8 and SAMP10 mice [J]. Neurochem Res, 2009, 34(4): 639-659.
[15] 马芹颖,强静,王铭维. 快速老化小鼠SAMP8脑内神经病理学变化的研究进展[J]. 中国老年学杂志, 2011, 31(19): 3858-3860.
[16] Manich G, Mercader C, del Valle J, et al. Characterization of amyloid-β granules in the hippocampus of SAMP8 mice [J]. J Alzheimers Dis, 2011, 25(3): 535-546.
[17] Morley JE, Farr SA, Kumar VB, et al. The SAMP8 mouse: a model to develop therapeutic interventions for Alzheimer's disease [J]. Curr Pharm Des, 2012, 18(8): 1123-1130.
[18] Huang KY, Liang S, Yu ML, et al. A systematic review and meta-analysis of acupuncture for improving learning and memory ability in animals [J]. BMC Complement Altern Med, 2016, 16(1): 297.
[19] Li G, Zhang X, Cheng H, et al. Acupuncture improves cognitive deficits and increases neuron density of the hippocampus in middle-aged SAMP8 mice [J]. Acupunct Ned, 2012, 30(4): 339-345.
[20] 李向宇,徐乐,柳垂亮,等. 电针对异氟醚引起的APPswe/PS1dE9小鼠学习记忆能力及海马激活型Caspase-3、Bcl-2/Bax变化的影响[J]. 针刺研究, 2016, 41(1): 24-30.
[21] 张永杰,唐冬梅,徐桂萍. 突触可塑性分子机制的相关研究[J]. 医学综述, 2012, 18(8): 1141-1143.
[22] Kwon SE, Chapman ER. Synaptophysin regulates the kinetics of synaptic vesicle endocytosis in central neurons [J]. Neuron, 2011, 70(5): 847-854.
[23] Pan W, Han S, Kang L, et al. Effects of dihydrotestosterone on synaptic plasticity of the hippocampus in mild cognitive impairment males SAMP8 mice [J]. Exp Ther Med, 2016, 12(3): 1455-1463.
[24] Wang J, Yuan J, Pang J, et al. Effects of chronic stress on cognition in male SAMP8 mice [J]. Cell Physiol Biochem, 2016, 39(3): 1078-1086.
[25] 于萍,袁水霞,李霞,等. 记忆过程中海马CA1区神经元的集群放电特征[J]. 心理学报, 2011, 43(8): 917-928.
[26] 张亢亢,孔立红,王颖,等. 不同频率电针对AD大鼠海马CA1区突触素和PSD-95表达的影响[J]. 时珍国医药, 2016, 27(10): 2539-2542.
[27] 余曙光,罗松,韩婷,等. 电针对老年性痴呆大鼠海马神经元突触形态可塑性的影响研究[J]. 中华神经医学杂志, 2006, 5(4): 369-371.
[28] 王威,唐伟,孙忠人. 电针对拟老年性痴呆大鼠学习记忆功能和海马CA1区突触表达的影响[J]. 中国中医药科技, 2011, 18(1): 1-2.
[29] 宋长明,黄佳,林冰冰,等. 电针百会、神庭穴对脑缺血再灌注大鼠学习记忆能力及海马CA1区突触超微结构的影响[J]. 中国康复理论与实践, 2017, 23(7): 750-755.