补肾活血针刺法对SAMP8小鼠学习记忆能力及海马内源性神经干细胞增殖的影响
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摘要
目的观察补肾活血针刺法对阿尔茨海默病(AD)模型SAMP8小鼠行为学及海马内源性神经干细胞增殖的影响。方法将18只7月龄雄性SAMP8小鼠作为AD模型,随机分为针刺组、非穴组和模型组,另取同月龄雄性SAMR1小鼠6只作为正常组。针刺组小鼠选取"肾俞""百会""血海""膈俞"进行针刺干预,非穴组小鼠取双侧肋下固定非穴点进行针刺,模型组和正常组小鼠予相同程度捉抓刺激,连续干预8周。采用水迷宫实验检测小鼠学习记忆能力,免疫组化检测海马Brd U阳性细胞数。结果与正常组比较,模型组小鼠逃避潜伏期明显延长(P<0.05),停留在原平台象限时间明显缩短(P<0.05),Brd U阳性细胞数明显减少(P<0.05);与模型组、非穴组比较,针刺组小鼠逃避潜伏期明显缩短(P<0.05),停留在原平台象限时间明显延长(P<0.05),Brd U阳性细胞数明显增加(P<0.05)。结论补肾活血针刺法可能通过诱导海马内源性神经干细胞的增殖,改善AD模型SAMP8小鼠的学习记忆能力。
Objective To investigate the effects of Bushen Huoxue acupuncture method on the behavioral changes and the proliferation of endogenous neural stem cells(NSCs) in hippocampus of Alzheimer disease(AD) model mice. Methods 18 male SAMP8 mice, seven months old, were randomly divided into acupuncture group, non-acupoint control group, and model control group. And another age-matched 6 male SAMR1 mice were prepared as normal control group. Mice in acupuncture group were intervened by acupuncture method in the acupoints of "Shenshu", "Baihui", "Xuehai", and "Geshu". Mice in non-acupoint control group were treated by stimulating the fixed non-point under the bilateral rib, while mice in model control group and normal control group were raised without special treatment but administered the stimulation of catching with the same time and the same stimulus intensity. All treatrment lasted for 8 weeks. After the intervention, the learning and memory abilitities and brain hippocampus Brd U positive cells of all groups were detected. Results Compared with the nomal control group, mice in the model control group had longer escape latency and less time spent in former platform quadrant(P<0.05); the number of Brd U positive cells decreased significantly(P<0.05). Compared with the model control group and the non-acupoint control group, mice in the acupuncture group had shorter escape latency and more time spent in former platform quadrant(P<0.05); the number of Brd U positive cells increased significantly(P<0.05). Conclusion Bushen Huoxue acupuncture method can improve the learning and memory abilities of SAMP8 mice AD model by inducing the proliferation of hippocampal endogenous NSCs.
Objective To investigate the effects of Bushen Huoxue acupuncture method on the behavioral changes and the proliferation of endogenous neural stem cells(NSCs) in hippocampus of Alzheimer disease(AD) model mice. Methods 18 male SAMP8 mice, seven months old, were randomly divided into acupuncture group, non-acupoint control group, and model control group. And another age-matched 6 male SAMR1 mice were prepared as normal control group. Mice in acupuncture group were intervened by acupuncture method in the acupoints of "Shenshu", "Baihui", "Xuehai", and "Geshu". Mice in non-acupoint control group were treated by stimulating the fixed non-point under the bilateral rib, while mice in model control group and normal control group were raised without special treatment but administered the stimulation of catching with the same time and the same stimulus intensity. All treatrment lasted for 8 weeks. After the intervention, the learning and memory abilitities and brain hippocampus Brd U positive cells of all groups were detected. Results Compared with the nomal control group, mice in the model control group had longer escape latency and less time spent in former platform quadrant(P<0.05); the number of Brd U positive cells decreased significantly(P<0.05). Compared with the model control group and the non-acupoint control group, mice in the acupuncture group had shorter escape latency and more time spent in former platform quadrant(P<0.05); the number of Brd U positive cells increased significantly(P<0.05). Conclusion Bushen Huoxue acupuncture method can improve the learning and memory abilities of SAMP8 mice AD model by inducing the proliferation of hippocampal endogenous NSCs.
引文
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[8]王卫东,王洪典,王冰,等.反映成年大鼠脑组织神经发生水平显示方法的灵敏性和可靠性评价[J].中国临床康复,2002,6(13):1502-1507.
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[10]张学婷,张磊,周英奕,等.电针“百会”“涌泉”穴对APP/PS1双转基因小鼠海马β淀粉样蛋白及载脂蛋白E水平的影响[J].针灸临床杂志,2017,33(12):73-77.
[11]张翠翠.针刺对AD模型大鼠海马凋亡相关蛋白Caspase-3的影响[J].四川生理科学杂志,2014,36(2):62-63.
[12]LI G,ZHANG X,CHENG H,et al.Acupuncture improves cognitive deficits and increases neurondensity of the hippocampus in middle-aged SAMP8 mice[J].Acupunct Med,2012,30(4):339-345.
[13]LIN R H,CHEN J X,LI X J,et al.Electroacupuncture at the Baihui acupoint alleviates cognitive impairment and exerts neuroprotective effects by modulating the expression and processing of brain derived neurotrophic factor in APP/PS1transgenic mice[J].Molecular Medicine Reports,2016,13:1611-1617.
[14]卓沛元,柳维林,吴洁,等.电针百会穴对APP/PS1双转基因痴呆模型小鼠18F-FDG PET/CT成像及学习记忆的影响[J].中国康复医学杂志,2016,31(10):1050-1053.
[15]赵建新,田元祥,曹刚,等.电针肾俞、膈俞、百会穴对拟血管性痴呆小鼠脑缺血、缺氧、脑水肿的影响[J].中国中医基础医学杂志,2000,6(6):60-64.
[16]张玮,苏利强,赵广高,等.针刺血海穴对反复力竭游泳大鼠血清IFN-γ和IL-4影响的研究[J].时珍国医国药,2011,22(12):3019-3021.
[17]梁梅亭,朱宏,董克礼,等.补肾活血针刺法对SAMP8小鼠杏仁核蛋白质组学表达的影响[J].中国中医药信息杂志,2018,25(3):58-63.
[2]朱宏,董克礼,吴岳.补肾活血法对阿尔茨海默病患者认知功能改善的影响[J].中国老年杂志,2010,30(11):1493-1495.
[3]戴思思,董克礼,朱宏.“补肾活血”针刺法对老年性痴呆模型SAMP8小鼠学习记忆能力和脑组织ACh E活性的影响[J].上海针灸杂志,2010,29(1):57-59.
[4]朱宏,董克礼,李广城,等.“补肾活血”针刺法对SAMP8小鼠海马蛋白质表达的影响[J].中国老年学杂志,2011,31(23):4613-4461.
[5]李忠仁.实验针灸学[M].北京:中国中医药出版社,2003:327.
[6]卞金玲,张春红.石学敏院士针刺手法量学的概念及核心[J].中国针灸,2003,23(5):287-289.
[7]吴帮启,刘存志,于建春,等.针刺研究中假针刺组的设置概况[J].上海针灸杂志,2009,28(1):59-61.
[8]王卫东,王洪典,王冰,等.反映成年大鼠脑组织神经发生水平显示方法的灵敏性和可靠性评价[J].中国临床康复,2002,6(13):1502-1507.
[9]韩向博,王鑫,姜婧,等.电针对SAMP8小鼠海马区PS1蛋白表达的影响[J].现代生物医学进展,2015,15(22):4225-4229,4234.
[10]张学婷,张磊,周英奕,等.电针“百会”“涌泉”穴对APP/PS1双转基因小鼠海马β淀粉样蛋白及载脂蛋白E水平的影响[J].针灸临床杂志,2017,33(12):73-77.
[11]张翠翠.针刺对AD模型大鼠海马凋亡相关蛋白Caspase-3的影响[J].四川生理科学杂志,2014,36(2):62-63.
[12]LI G,ZHANG X,CHENG H,et al.Acupuncture improves cognitive deficits and increases neurondensity of the hippocampus in middle-aged SAMP8 mice[J].Acupunct Med,2012,30(4):339-345.
[13]LIN R H,CHEN J X,LI X J,et al.Electroacupuncture at the Baihui acupoint alleviates cognitive impairment and exerts neuroprotective effects by modulating the expression and processing of brain derived neurotrophic factor in APP/PS1transgenic mice[J].Molecular Medicine Reports,2016,13:1611-1617.
[14]卓沛元,柳维林,吴洁,等.电针百会穴对APP/PS1双转基因痴呆模型小鼠18F-FDG PET/CT成像及学习记忆的影响[J].中国康复医学杂志,2016,31(10):1050-1053.
[15]赵建新,田元祥,曹刚,等.电针肾俞、膈俞、百会穴对拟血管性痴呆小鼠脑缺血、缺氧、脑水肿的影响[J].中国中医基础医学杂志,2000,6(6):60-64.
[16]张玮,苏利强,赵广高,等.针刺血海穴对反复力竭游泳大鼠血清IFN-γ和IL-4影响的研究[J].时珍国医国药,2011,22(12):3019-3021.
[17]梁梅亭,朱宏,董克礼,等.补肾活血针刺法对SAMP8小鼠杏仁核蛋白质组学表达的影响[J].中国中医药信息杂志,2018,25(3):58-63.