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中国应用生理学杂志 ›› 2019, Vol. 35 ›› Issue (4): 359-362.doi: 10.12047/j.cjap.5797.2019.076

• 研究论文 • 上一篇    下一篇

小檗碱对血管性认知功能障碍模型大鼠学习记忆能力的影响*

王汝欢1, 周茹2, 丁洋3, 周振兴4△   

  1. 1. 深圳信立泰药业股份有限公司, 广东 深圳 518102;
    2. 首都医科大学附属北京地坛医院 检验科, 北京 100015;
    3. 首都医科大学附属北京中医医院 消化中心, 北京 100010;
    4. 首都医科大学附属北京中医医院 检验科, 北京 100010
  • 收稿日期:2018-12-19 出版日期:2019-07-28 发布日期:2019-11-06
  • 通讯作者: ,Tel: 18201048920; E-mail: zzx0406@126.com
  • 基金资助:
    *北京市自然科学基金资助项目(7164265);国家自然科学基金资助项目(81400560)

Effects of berberine on learning and memory ability in vascular cognitive impairment rats

WANG Ru-huan1, ZHOU Ru2, DING Yang3, ZHOU Zhen-xing4△   

  1. 1. Shenzhen Salubris Pharmaceutical Co., Ltd, Shenzhen 518102;
    2. Department of Clinical Laboratory, Beijing Ditan Hospital Affiliated to Capital Medical University, Beijing 100015;
    3. Digestive Center, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010;
    4. Department of Clinical Laboratory, Beijing Traditional Chinese Medicine Hospital Affiliated to Capital Medical University, Beijing 100010, China
  • Received:2018-12-19 Online:2019-07-28 Published:2019-11-06

摘要: 目的:观察小檗碱(berberine)对血管性认知功能障碍(VCI)大鼠学习记忆的影响。 方法:68只Wistar大鼠随机分为:正常组10只、 假手术组10只、造模组48只。造模组大鼠行双侧颈动脉结扎术制备血管性认知功能障碍模型,造模后大鼠又随机分为血管性认知功能障模型组、小檗碱低剂量(20 mg/kg)组、中剂量(40 mg/kg)组和高剂量(60 mg/kg)组(每组大鼠10只)。治疗组腹腔注射不同剂量的小檗碱,其余组腹腔注射生理盐水,每天1次,共34 d。给药28 d后,Morris水迷宫检测大鼠学习记忆能力;水迷宫实验后,检测超氧化物歧化酶(SOD)活性和谷胱甘肽(GSH)、丙二醛(MDA)以及前脑皮层TNF-α、IL-1β、5-HT的含量与单胺氧化酶(MAO)的含量。 结果:与假手术组比较,模型组大鼠逃避潜伏期显著延长(P<0.01),通过平台次数显著减少(P<0.01),海马或前脑皮层SOD、GSH和5-HT水平明显降低(P<0.01),MDA、TNF-α、IL-1β和MAO水平明显升高(P<0.01);与模型组相比,小檗碱各治疗组逃避潜伏期显著缩短(P<0.01,P<0.05),通过平台的次数显著增加(P<0.01,P<0.05),海马或前脑皮层SOD、GSH 和5-HT水平明显升高(P<0.01),MDA、TNF-α、IL-1β和MAO水平明显降低(P<0.01)。结论:小檗碱显著提高血管性认知功能障碍模型大鼠的空间学习记忆能力,其机制可能与小檗碱调节大鼠的海马抗氧化应激、抗炎性反应和前脑皮层单胺类神经递质系统的作用有关。小檗碱60 mg/kg组作用较好。

关键词: 大鼠, 小檗碱, 血管性认知功能障碍, 氧化应激, 单胺类神经递质, 学习记忆

Abstract: Objective: To investigate the effects of berberine on learning and memory ability in vascular cognitive impairment rats. Methods: Sixty-eight Wistar rats were randomly divided into control group (n=10), sham operated group (n=10) and the modeling group of vascular cognitive impairment rat (n=48), then the rats in modeling group were randomly divided into four groups (n=10): vehicle group, berberine low dose group (20 mg/kg), medium dose group (40 mg/kg) and high dose group (60 mg/kg). Bilateral common carotid arteries were occluded in rats to establish vascular cognitive impairment (VCI) model. Different doses of berberine were intraperitoneally injected into the treatment group and normal saline was intraperitoneally injected into the other groups once a day for a total of 34 days. After 28 days of administration, Morris water maze was used to test the learning and memory ability of rats. After the water maze experiment, the levels of superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor alpha(TNF-α), interleukin-1 beta (IL-1β), 5-hydroxytryptamine (5-HT) and monoamine oxidase (MAO) in the forebrain cortex were detected. Results: Compared to sham group, the escape latency in VCI group was significantly extended (P<0.01) and the times of passing through the platform were decreased remarkably (P<0.01). The levels of SOD, GSH and 5-HT in the hippocampus or anterior cortex were decreased significantly (P<0.01), while the contents of MDA, TNF-α, IL-1β and MAO were increased remarkably (P<0.01). Compared with VCI group, the escape latency in berberine-treated groups was shortened significantly (P<0.01, P<0.05) and the times of passing through the platform were increased remarkably (P<0.01, P<0.05), the levels of SOD, GSH and 5-HT were increased significantly (P<0.01), while the contents of TNF-α, IL-1β and MAO were decreased remarkably (P<0.01). Conclusion: Berberine could significantly improve the spatial learning and memory abilities of rats with vascular cognitive impairment. The mechanism may be related to the effects of berberine on the hippocampal antioxidant stress, anti-inflammatory response and the monoamine neurotransmitter system in the forebrain cortex. Berberine 60 mg/kg dose group had better effect.

Key words: rats, berberine, vascular cognitive impairment, oxidative stress, monoamine transmitter, learning and memory

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