Chinese Medical Sciences Journal ›› 2018, Vol. 33 ›› Issue (1): 29-37.doi: 10.24920/11802

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  1. 1陕西中医药大学病理教研室,陕西咸阳 712046
    2西安交通大学附属西安市中心医院神经内科,西安 710003
    3约克大学生物学系,加拿大 多伦多 M3J 1P3
    4中国医学科学院 基础医学研究所 生物化学与分子生物学系 医学分子生物学国家重点实验室,北京 100005
  • 收稿日期:2017-06-02 出版日期:2018-02-13 发布日期:2018-02-13
  • 通讯作者: 彭小忠

Astragaloside IV Protects Against Aβ1-42-induced Oxidative Stress, Neuroinflammation and Cognitive Impairment in Rats

Pan Yanfang1,Jia Xiaotao2,Song Erfei3,Peng Xiaozhong4,*()   

  1. 1Department of Pathology, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, China
    2Department of Neurology, The Affiliated Xi'an Central Hospital of Xi'an Jiaotong University College of Medicine, Xi'an 710003, China;
    3 Department of Biology, York University, Toronto, ON M3J 1P3, Canada
    4State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing 100005, China;
  • Received:2017-06-02 Published:2018-02-13 Online:2018-02-13
  • Contact: Peng Xiaozhong
  • About author:This study investigated the neuroprotective action of astragaloside Ⅳon spatial learning and memory impairment induced by amyloid-beta 1-42 in rats and elucidated its underlying molecular mechanisms.

摘要: 目的 探讨黄芪甲苷拮抗淀粉样β蛋白(Aβ1-42)所致大鼠学习记忆损害的神经保护作用以及可能的分子机制。方法 成年Wistar雄性大鼠(体重230~250 g)被随机分为对照组、Aβ1-42、黄芪甲苷、(5,25和50 mg/kg·d)黄芪甲苷+Aβ1-42等6组。在脑立体定位仪引导下给大鼠侧脑室注射Aβ1-42。Aβ1-42 注射一周后进行Morris水迷宫实验(水下平台实验,空间探索实验,可见平台实验),以评估大鼠的空间学习记忆能力。Aβ1-42 注射后第8天开始腹腔注射黄芪甲苷(5,25和50 mg/kg·d), 连续注射5天。通过行为学软件记录大鼠寻找水下平台的平均逃避潜伏期、逃避距离、以及撤除平台后大鼠在目标象限内的游泳时间和距离百分比。同时测量大鼠的视力和游泳速度,以排除这些因素对记忆能力的影响。行为学实验后,大鼠被处死取出海马,然后测量不同处理组海马组织中的过氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-px)和过氧化氢酶(CAT)活性。采用ELISA测量海马组织中白介素1β(IL-1β)及肿瘤坏死因子-α(TNF-α) 的水平。结果 水迷宫实验结果显示 :通过慢性给药,黄芪甲苷能够有效保护大鼠的学习记忆能力免受Aβ1-42损害。同时,黄芪甲苷能够有效拮抗Aβ1-42 所致大鼠海马组织SOD、GSH-px和CAT的活性下降。另外,黄芪甲苷能显著降低Aβ1-42激发的大鼠海马组织中IL-1β和TNF-α的水平。结论 黄芪甲苷能改善阿尔兹海默病模型大鼠的空间记忆能力、降低患者脑组织中的氧化应激和神经炎症反应水平。

关键词: 淀粉样β蛋白, 黄芪甲苷, 学习记忆, 氧化应激, 神经炎症

Abstract: Objective To investigate the neuroprotective action of astragaloside IV (AS-IV) on spatial learning and memory impairment induced by amyloid-beta 1-42 (Aβ1-42) in rats and elucidate its underlying molecular mechanisms. Methods Adult-male Sprague-Dawley rats (230-250 g) were divided into six groups randomly: control, Aβ1-42, AS-IV, Aβ1-42 plus 5 mg/kg·d AS-IV, Aβ1-42 plus 25 mg/kg·d AS-IV, and Aβ1-42 plus 50 mg/kg·d AS-IV groups. Aβ1-42 were delivered by intracerebroventricular injection under the guidance of a brain stereotaxic apparatus. The Morris water maze test (hidden platform test, probe trials, visible platform test) was performed one week after Aβ1-42 injection to obtain the ability of rat spatial learning and memory. AS-IV (5, 25 and 50 mg/kg·d) was administrated intraperitoneally once per day from the 8th day after Aβ1-42 injection for 5 consecutive days. Average escape latencies, distances for searching for the platform under water and the percentage of total time elapsed and distance swam in the right quadrant after removing platform were determined by behavior software system. The vision and swim speeds of rats were also determined to exclude the effect of these factors on the parameters of learning and memory. After behavioral tests, the rats were sacrificed immediately by decapitation. Hippocampus were collected. The enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and catalase (CAT) in the hippocampus obtained from different-treated rat brain were measured by following the manufacturer’s instructions. The levels of interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in tissue lysates were assayed with ELISA. Results The water maze test results indicated that chronic treatments with AS-IV effectively protected the rats from Aβ1-42-induced spatial learning and memory impairment. Furthermore, the activities of SOD, GSH-px and CAT decreased by Aβ1-42 were also restored by AS-IV treatment in the hippocampus of rats. In addition, AS-IV significantly decreased the levels of IL-1β and TNF-α in the hippocampus of Aβ1-42-induced amnesia’s rats.Conclusion Our findings suggest that AS-IV might be a useful chemical in improving the spatial memory and relieving the oxidative stress and neuroinflammation in Alzheimer patients.

Key words: amyloid-β protein, astragaloside IV, spatial learning and memory, oxidative stress, neuroinflammation

基金资助: the Natural Science Foundation of Shaanxi Province of China(81703842);National Science Foundation of China(81703842)

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