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国际中医中药杂志20153月第37卷第3Int J Trad Chin Med, March 2015, Vol. 37, No.3 ·239· ·论著· 天芪益智颗粒对阿尔茨海默病模型大鼠 脑组织氧化应激和学习记忆的影响 赵军 武义明 马涛 卫东锋 【摘要】 目的 探讨天芪益智颗粒对阿尔茨海默病(alzheimer’s disease, AD)大鼠学习记忆的保护 作用及对脑组织氧化应激的影响。方法 90 只雄性 SD 大鼠按随机数字表法分为假手术组,模型组,石 杉碱甲组以及天芪益智低、中、高剂量组,每组 15 只。右侧侧脑室注射 β-淀粉样多肽 1-42 (Aβ 1-42 )制备 AD 模型。造模 1 周后开始给药,天芪益智颗粒高、中、低剂量组分别灌胃天芪益智颗粒溶液生药含量分别 0.81.6 3.2 g/kg;石杉碱甲组灌胃石杉碱甲溶液 0.02 mg/kg;假手术组和模型组灌胃等体积生理盐 水。连续灌胃给药 30 d。采用避暗实验检测大鼠学习记忆能力。检测脑组织超氧化物歧化酶(SOD)、谷胱 甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)水平。结果 与模型组比较,天芪益智颗粒高、中剂量 组进入暗室的潜伏期显著延长[(239.05±48.42)s、(214.35±74.52)s 比(97.39±30.69sP 均<0.01],错 误次数显著减少[分别为(1.93±3.25)次、(2.27±3.09)次比(6.62±3.45)次;P 均<0.05],脑组织 SOD[(177.27±63.10)U/mg、(164.53±72.58)U/mg 比(72.56±21.04)U/mgP 均<0.01]和 GSH-Px [(2 899.36±362.27)U/g、(2 407.68±472.14)U/g 比(1 397.64±442.17)U/gP 均<0.01]活性显著增高, MDA 水平[(24.75±9.94)nmol/mg、(27.74±5.82)nmol/mg 比(37.56±17.23)nmol/mgP 均<0.01]显著 降低。结论 天芪益智颗粒可减轻 AD 大鼠脑组织氧化应激,改善学习记忆。 关键词阿尔茨海默病;学习;记忆;氧化性应激;大鼠;天芪益智颗粒 Effects of Tianqi-Yizhi granules on oxidative stress in the brain tissue, and learning and memory in Alzheimer's disease model rats Zhao Jun * , Wu Yiming, Ma Tao, Wei Dongfeng. * Worker Hospital of Xuanhua Steel Company, Hebei Iron & Steel Group, Zhangjiakou 075100, China Corresponding author: Ma Tao, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100078, China; Email: [email protected] AbstractObjective To investigate the effects of Tianqi-Yizhi granules on oxidative stress in the brain tissue, and learning and memory in Alzheimer's disease model rats. Methods A total of 90 male SD rats were randomly divided into 6 groups by random number table method: sham operation group, model group, huperzine A group and groups of low-, medium- and high-dose Tianqi-Yizhi granules, with 15 rats in each group. The AD rat model was prepared by the left lateral ventricle injection of amyloid-β 1-42 . One week after modeling, the rats in the groups of low-, medium- and high-dose Tianqi-Yizhi granules received intragastric administration of 0.8, 1.6 and 3.2 g/kg Tianqi-Yizhi granules, respectively; the rats in the huperzine A group received intragastric administration of 0.02 mg/kg huperzine A solution; and the rats in the sham operation and model groups received intragastric administration of equivalent volume of normal saline for 30 days. Learning and memory were evaluated using the dark avoidance test. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and malonaldehyde (MDA) level in the brain tissue were determined. Results In comparison with the model group, the latencies to step into the dark chamber in the high- and DOI: 10.3760/cma.j.issn.1673-4246.2015.03.013 基金项目:国家科技重大专项-重大新药创制(2013ZX09103002-002);国家自然科学基金重点项目(81430100作者单位:075100 张家口,河北钢铁集团宣化钢铁公司职工医院老年病科(赵军),放射科(武义明);100078 北京中医药大学东方医院实验中心(马涛);100875 北京师范大学老年脑健康研究中心(马涛、卫东锋) 通信作者:马涛,Email: [email protected]

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天芪益智颗粒对阿尔茨海默病模型大鼠 脑组织氧化应激和学习记忆的影响

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  • 20153373 Int J Trad Chin Med, March 2015, Vol. 37, No.3 239

    alzheimers disease, AD 90 SD 15 - 1-42(A1-42) AD 1 0.81.6 3.2 g/kg 0.02 mg/kg 30 dSODGSH-PxMDA [(239.0548.42)s(214.3574.52)s (97.3930.69sP 0.01][(1.933.25)(2.273.09)(6.623.45)P 0.05]SOD[(177.2763.10)U/mg(164.5372.58)U/mg (72.5621.04)U/mgP 0.01] GSH-Px [(2 899.36362.27)U/g(2 407.68472.14)U/g (1 397.64442.17)U/gP 0.01]MDA [(24.759.94)nmol/mg(27.745.82)nmol/mg (37.5617.23)nmol/mgP 0.01] AD

    Effects of Tianqi-Yizhi granules on oxidative stress in the brain tissue, and learning and memory in Alzheimer's disease model rats Zhao Jun*, Wu Yiming, Ma Tao, Wei Dongfeng. *Worker Hospital of Xuanhua Steel Company, Hebei Iron & Steel Group, Zhangjiakou 075100, China Corresponding author: Ma Tao, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100078, China; Email: [email protected]

    Abstract Objective To investigate the effects of Tianqi-Yizhi granules on oxidative stress in the brain tissue, and learning and memory in Alzheimer's disease model rats. Methods A total of 90 male SD rats were randomly divided into 6 groups by random number table method: sham operation group, model group, huperzine A group and groups of low-, medium- and high-dose Tianqi-Yizhi granules, with 15 rats in each group. The AD rat model was prepared by the left lateral ventricle injection of amyloid-1-42. One week after modeling, the rats in the groups of low-, medium- and high-dose Tianqi-Yizhi granules received intragastric administration of 0.8, 1.6 and 3.2 g/kg Tianqi-Yizhi granules, respectively; the rats in the huperzine A group received intragastric administration of 0.02 mg/kg huperzine A solution; and the rats in the sham operation and model groups received intragastric administration of equivalent volume of normal saline for 30 days. Learning and memory were evaluated using the dark avoidance test. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and malonaldehyde (MDA) level in the brain tissue were determined. Results In comparison with the model group, the latencies to step into the dark chamber in the high- and

    DOI: 10.3760/cma.j.issn.1673-4246.2015.03.013

    2013ZX09103002-00281430100 075100 100078

    100875 Email: [email protected]

  • 240 20153373 Int J Trad Chin Med, March 2015, Vol. 37, No.3

    medium-dose Tianqi-Yizhi granules groups were significantly longer (239.05 48.42 s, 214.35 74.52 s vs. 97.39 30.69 s; all P

  • 20153373 Int J Trad Chin Med, March 2015, Vol. 37, No.3 241

    A1-42 AD 1 3.21.60.8 g/kg 0.02 mg/kg 30 d 1.6 2 h 2 1 5 min 24 h 1.7 RIPA 4 10 000 r/min BCA SODGSH-PX MDA 1.8 SPSS13.0 sx one-way ANOVA Post Hoc P0.05

    2 2.1 30 dP0.01

    P0.05 P0.01P0.05 1 1 ( sx )

    (mg/kg) (s)

    ()

    15 276.3459.29 0.731.21 15 97.3930.69a 6.623.45a 15 0.02 225.8269.03b 1.723.90c

    15 3 200 239.0548.42b 1.933.25c

    15 1 600 214.3574.52b 2.273.09c

    15 800 194.2133.04b 5.432.32

    aP0.01bP0.01cP0.05 2.2 SODGSH-PX MDA P0.01SODGSH-PX MDA P0.05 P0.01 2

    3

    A1-42

    2 SODMDAGSH-PX ( sx ) (mg/kg) SOD (U/mg) MDA(nmol/mg) GSH-PX (U/g)

    6 243.2647.65 22.63 8.86 3 572.12543.29 6 72.5621.04a 37.5617.23a 1 397.64442.17a 6 0.02 146.0354.04b 33.4214.05c 1 647.05329.77 6 3 200 177.2763.10b 24.75 9.94b 2 899.36362.27b 6 1 600 164.5372.58b 27.74 5.82b 2 407.68472.14b 6 800 132.4969.14c 35.05 9.43c 2 409.39448.93b

    SODMDAGSH-PXaP0.01bP0.01cP0.05

  • 242 20153373 Int J Trad Chin Med, March 2015, Vol. 37, No.3

    A1-42 AD

    AD AD AD [5] SODGSH-PX [6] AD A AD A A1-40 A1-42 A1-42 A AD A [7]A [6-7] A AD [8-9] A1-42 AD

    [3-4] AD

    AD

    1 Cervellati C,Romani A,Seripa D,et al. Oxidative balance,

    homocysteine,and uric acid levels in older patients with Late Onset Alzheimer's Disease or Vascular Dementia[J]. J Neurol Sci,2014,337(1/2):156-161.

    2 . [J]. ,2011,52(19):1627-1629.

    3 ,. Alzheimer [J]. ,2011,42(9):5-7.

    4 . [M]. 4 . ,2010:686.

    5 Nunonura A,Perry G,Aliev G,et al. Oxidative damage is the earliest event in Alzhimer disease[J]. J Neuropathol Exp Neurol,2001,60(8):759-767.

    6 Aliev G,Priyadarshini M,Reddy VP,et al. Oxidative stress mediated mitochondrial and vascular lesions as markers in the pathogenesis of Alzheimer disease[J]. Curr Med Chem,2014, 21(19):2208-2217.

    7 Balducci C,Mancini S,Minniti S,et al. Multifunctional Liposomes Reduce Brain -Amyloid Burden and Ameliorate Memory Impairment in Alzheimer's Disease Mouse Models[J]. J Neurosci,2014,34(42):14022-14031.

    8 Zhang LL,Sui HJ,Liang B,et al. Atorvastatin prevents amyloid- peptide oligomer-induced synaptotoxicity and memory dysfunction in rats through a p38 MAPK-dependent pathway[J]. Acta Pharmacol Sin,2014,35(6):716-726.

    9 Cunha GM,Canas PM,Melo CS,et al. Adenosine A2A receptor blockade prevents memory dysfunction caused by beta-amyloid peptides but not by scopolamine or MK-801[J]. Exp Neurol,2008,210(2):776-781.

    2014-11-05