电针对不同阶段SAMP8小鼠学习记忆能力、神经元超微结构及β-淀粉样蛋白、Tau蛋白水平的影响
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摘要
目的观察电针"百会""大椎""肾俞"对3月龄及9月龄SAMP8小鼠学习记忆能力及海马区β-淀粉样蛋白(Aβ)、Tau蛋白表达的影响,探讨电针治疗阿尔茨海默病的时机。方法将SAMP8小鼠随机分为早期电针组(3月龄电针干预)、晚期电针组(9月龄电针干预)、模型组,以同龄正常老化SAMR1小鼠为对照组,并均于10月龄取材。采用Morris水迷宫实验检测小鼠学习记忆能力,透射电镜观察小鼠海马CA1区神经超微结构变化,免疫组化检测小鼠海马区Aβ、Tau蛋白的表达。结果与晚期电针组比较,早期电针组小鼠逃避潜伏期明显缩短(P<0.05),原平台象限停留时间明显延长(P<0.05),跨越原平台次数明显增加(P<0.05),海马区Aβ、Tau蛋白异常表达明显减少(P<0.05),突触结构较完整,数量增加。结论电针能提高SAMP8小鼠学习记忆能力,降低小鼠海马区Aβ、Tau蛋白的异常表达,改善神经元超微结构,且其疗效早期介入优于晚期介入。
Objective To observe the effects of electroacupuncture(EA) "Baihui", "Dazhui", and "Shenshu" on learning memory ability, ultrastructure of neurons, and expressions of Aβ and Tau in three-month old and nine-month old SAMP8 mice; To discuss the timing of EA for the treatment of Alzheimer disease(AD). Methods SAMP8 mice were randomly divided into three groups: early-stage-EA group(3-month-old EA), advanced-stage-EA group(9-month-old EA) and model group. Normally aged SAMR1 mice of the same age were set as the control group. Finally all mice were sacrificed in ten-month old. The learning and memory ability of mice was detected by Morris water maze test. The ultrastructural changes of hippocampal CA1 region were observed by transmission electron microscopy. The expressions of Aβ and Tau in hippocampus of mice were detected by immunohistochemistry. Results Compared with the advanced-stage-EA group, the escape latency of the early-stage-EA group was significantly shortened(P<0.05); the time spent in target quadrant was prolonged(P<0.05); the number of crossing was expanded(P<0.05); the aberrant expressions of Aβ and Tau in hippocampal CA1 region was attenuated(P<0.05); synaptic structure was more complete and the synaptic number increased. Conclusion EA can improve the learning and memory ability of SAMP8 mice, reduce the abnormal expressions of Aβ and Tau protein in hippocampus of mice, and ameliorate the ultrastructure of neurons. Especially the early intervention is superior to the late intervention.
Objective To observe the effects of electroacupuncture(EA) "Baihui", "Dazhui", and "Shenshu" on learning memory ability, ultrastructure of neurons, and expressions of Aβ and Tau in three-month old and nine-month old SAMP8 mice; To discuss the timing of EA for the treatment of Alzheimer disease(AD). Methods SAMP8 mice were randomly divided into three groups: early-stage-EA group(3-month-old EA), advanced-stage-EA group(9-month-old EA) and model group. Normally aged SAMR1 mice of the same age were set as the control group. Finally all mice were sacrificed in ten-month old. The learning and memory ability of mice was detected by Morris water maze test. The ultrastructural changes of hippocampal CA1 region were observed by transmission electron microscopy. The expressions of Aβ and Tau in hippocampus of mice were detected by immunohistochemistry. Results Compared with the advanced-stage-EA group, the escape latency of the early-stage-EA group was significantly shortened(P<0.05); the time spent in target quadrant was prolonged(P<0.05); the number of crossing was expanded(P<0.05); the aberrant expressions of Aβ and Tau in hippocampal CA1 region was attenuated(P<0.05); synaptic structure was more complete and the synaptic number increased. Conclusion EA can improve the learning and memory ability of SAMP8 mice, reduce the abnormal expressions of Aβ and Tau protein in hippocampus of mice, and ameliorate the ultrastructure of neurons. Especially the early intervention is superior to the late intervention.
引文
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[16] DEL V J, DURAN-VILAREGUT J, MANICH G, et al. Early amyloid accumulation in the hippocampus of SAMP8 mice[J]. Journal of Alzheimers Disease Jad,2010,19(4):1303.
[17]王鑫,加吾拉·阿不力孜,李芙,等.电针对APP/PS1双转基因小鼠行为学及皮层Aβ1-42、LRP1表达的影响[J].中华中医药杂志,2015,30(5):1513-1518.
[18]薛卫国,张忠,许红,等.电针对淀粉样前体蛋白转基因小鼠海马微血管淀粉样沉积的影响及其与低密度脂蛋白相关受体1的关系[J].针刺研究,2011,36(2):95-100.
[19]郎尉雅,张海燕,刘忠锦.电针对SAMP8小鼠行为学及APPmRNA和BACE-1mRNA影响[J].中国临床解剖学杂志,2015,33(5):563-567.
[20]刘丹,张子凡,赵小康.督脉电针早期干预对慢性脑缺血大鼠IL-1β和TNF-α表达的影响[J].辽宁中医杂志,2014,41(9):1844-1845.
[21]肖娜,向珩,黄力平,等.早期穴位电针治疗对局灶性脑缺血大鼠脑缺血皮质胰岛素样生长因子-1表达的影响[J].中华物理医学与康复杂志,2014,36(1):16-20.
[2] QUERTURTH H W, LAFERLA F M. Alzheimer's disease[J]. N Engl J Med,2010,362(4):329-344.
[3] SHENG M, SABATINI B L, SüDHOF T C, et al.[Molecular Pathology]SynapsesandAlzheimer'sdisease[J].ColdSpringHarbor Perspectives in Biology,2012,4(5):747-749.
[4]SELKOEDJ.Alzheimer'sdiseaseisasynapticfailure[J].Science,2002,298(5594):789-791.
[5]岳进,聂慧,李荣华.针灸治疗老年性痴呆的神经生物机制实验研究进展[J].上海针灸杂志,2009,28(3):183-185.
[6] CHENG H Y, YU J C, JIANG Z G, et al. Acupuncture improves cognitive deficits and regulates the brain cell proliferation of SAMP8 mice[J]. Neuroscience Letters,2008,26(8):111-116.
[7] DONG W G, WANG F, CHEN Y, et al. Electroacupuncture reduces Aβproduction and BACE1 expression in SAMP8 Mice[J]. Frontiers in Aging Neuroscience,2015,10(7):148-155.
[8]李斐斐,杨珺,杨文丹,等.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[J].中国康复理论与实践,2017,23(11):1278-1283.
[9]余曙光,郭义.实验针灸学[M].北京:人民卫生出版社,2012:252.
[10]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.
[11]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.
[12]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.
[13]沈峰,孙国杰,杜艳军,等.针灸从益肾调督论治老年痴呆探讨[J].湖北中医药大学学报,2013,15(2):44-46.
[14] YANAI S, ENDO S. Early onset of behavioral alterations in senescence-acceleratedmouseprone8(SAMP8)[J].Behavioural Brain Research,2016,308(4):187-195.
[15]CANUDASAM,GUTIERREZ-CUESTAJ,RODRíGUEZMI,etal.Hyperphosphorylation of microtubule-associated protein tau in senescence-accelerated mouse(SAM)[J]. Mechanisms of Ageing&Development,2005,126(12):1300.
[16] DEL V J, DURAN-VILAREGUT J, MANICH G, et al. Early amyloid accumulation in the hippocampus of SAMP8 mice[J]. Journal of Alzheimers Disease Jad,2010,19(4):1303.
[17]王鑫,加吾拉·阿不力孜,李芙,等.电针对APP/PS1双转基因小鼠行为学及皮层Aβ1-42、LRP1表达的影响[J].中华中医药杂志,2015,30(5):1513-1518.
[18]薛卫国,张忠,许红,等.电针对淀粉样前体蛋白转基因小鼠海马微血管淀粉样沉积的影响及其与低密度脂蛋白相关受体1的关系[J].针刺研究,2011,36(2):95-100.
[19]郎尉雅,张海燕,刘忠锦.电针对SAMP8小鼠行为学及APPmRNA和BACE-1mRNA影响[J].中国临床解剖学杂志,2015,33(5):563-567.
[20]刘丹,张子凡,赵小康.督脉电针早期干预对慢性脑缺血大鼠IL-1β和TNF-α表达的影响[J].辽宁中医杂志,2014,41(9):1844-1845.
[21]肖娜,向珩,黄力平,等.早期穴位电针治疗对局灶性脑缺血大鼠脑缺血皮质胰岛素样生长因子-1表达的影响[J].中华物理医学与康复杂志,2014,36(1):16-20.