Chinese Medical Sciences Journal ›› 2018, Vol. 33 ›› Issue (1): 29-37.doi: 10.24920/11802
黄芪甲苷拮抗Aβ1-42所致大鼠氧化应激,神经炎症和认知功能损伤
潘艳芳1,贾晓涛2,宋二飞3,彭小忠4,*(
)
- 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
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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 E-mail:pengxiaozhong@pumc.edu.cn
Astragaloside IV Protects Against Aβ1-42-induced Oxidative Stress, Neuroinflammation and Cognitive Impairment in Rats
Pan Yanfang1,Jia Xiaotao2,Song Erfei3,Peng Xiaozhong4,*()
- 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;
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Received:2017-06-02Published:2018-02-13Online:2018-02-13 -
Contact:Peng Xiaozhong E-mail:pengxiaozhong@pumc.edu.cn -
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。
引用本文
Pan Yanfang, Jia Xiaotao, Song Erfei, Peng Xiaozhong. Astragaloside IV Protects Against Aβ1-42-induced Oxidative Stress, Neuroinflammation and Cognitive Impairment in Rats[J].Chinese Medical Sciences Journal, 2018, 33(1): 29-37.
Figure 1.
Schematic diagram of drug treatment and behavioral tests.Aβ1-42 was injected into the intracerebroventricular of rats. After a recovery period for 7 days, AS-IV was intraperitoneally administrated at the doses of 5, 25 and 50 mg/kg·d respectively for 5 consecutive days. Aβ1-42: amyloid-beta 1-42; AS-IV: astragalosideIV."
Figure 1.
Figure 2.
AS-IV reatments attenuated Aβ1-42-induced spatial learning and memory impairment in rats. A. Rats with different treatments as labeled in the figure were trained for five consecutive days and the average escape latencies of rats were checked by the Morris water maze. B. The probe testing in various groups were performed four times per day and the percentages of total time in the target quadrant were calculated. C. Visible platform test was performed in rats with different treatments. D. The swimming speed (cm/s) in the various groups were evaluated. The data were represented as mean±SE. (n=10). *P<0.05 compared with the control group. #P<0.05, ##P<0.01 compared with the Aβ1-42 alone group."
Figure 2.
Figure 3.
AS-IV attenuated the oxidative stress in the hippocampus of rats treated with Aβ1-42. Rats were received different treatments as labeled in the figure for five days and the activities of superoxide dismutase (SOD, A), glutathione peroxidase (GSH-px, B) and catalase (CAT, C) in hippocampus were checked. Values were expressed as mean ± SE (n=8). **P<0.01 compared with the control group; #P<0.05, ##P<0.01 compared with the Aβ1-42 group."
Figure 3.
Figure 4.
AS-IV prevented the increase of IL-1β and TNF-α induced by Aβ1-42. ELISA for interleukin-1 beta (IL-1β, A) and tumor necrosis factor-alpha (TNF-α, B) were performed in the hippocampus tissue of rats with various treatments. Values are expressed as mean ± SE (n=8). **P<0.01 compared with the control group; #P<0.05, ##P<0.01 compared with the Aβ1-42 group."
Figure 4.
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