中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (2): 332-341.doi: 10.4103/1673-5374.265565

• 原著:退行性病与再生 • 上一篇    下一篇

番茄红素干预血管性痴呆大鼠学习记忆障碍的机制

  

  • 出版日期:2020-02-15 发布日期:2020-05-25
  • 基金资助:
    2013年中国国家创新创业培训项目（201310392009）; 2014年中国福建省创新创业培训项目（201410392058）

Possible mechanisms of lycopene amelioration of learning and memory impairment in rats with vascular dementia

Ning-Wei Zhu1, 2, Xiao-Lan Yin1, Ren Lin1, Xiao-Lan Fan1, Shi-Jie Chen1, Yuan-Ming Zhu1, Xiao-Zhen Zhao1, 3   

  1. 1 Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province, China
    2 Department of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, Zhejiang Province, China
    3 Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province, China
  • Online:2020-02-15 Published:2020-05-25
  • Contact: Xiao-Zhen Zhao, MS,zxz8338@163.com.
  • Supported by:
    This work was financially supported by the National Innovation and Entrepreneurship Training Project of China in 2013, No. 201310392009 (to XZZ); the Innovation and Entrepreneurship Training Project of Fujian Province of China in 2014, No. 201410392058 (to XZZ).

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摘要：

有研究表明，血管性痴呆的发病与氧化应激有关，而番茄红素能显著抑制氧化应激。为此，实验设计假设采用番茄红素可降低血管性痴呆中的氧化应激水平，并探讨其可能的机制。以永久性结扎双侧颈总动脉建立血管性痴呆大鼠模型，分别给予番茄红素(50，100和200 mg/kg)灌胃，隔日给药持续2个月，并设不结扎双侧颈总动脉的大鼠为假手术组。为了检测大鼠学习记忆能力，采用Morris水迷宫方法检测平均逃避潜伏期和搜索策略变化；采用苏木精-伊红染色法观察大鼠海马神经元变化；检测各组大鼠海马中氧化应激因子超氧化物歧化酶和丙二醛的水平变化；采用DHE染色法观察大鼠海马结构ROS活性变化；采用免疫荧光组织化学法和Western blot法检测大鼠海马神经元氧化应激相关蛋白-限制性沉默因子蛋白(NRSF)分布和表达水平。给药2个月后结果发现：(1)模型组大鼠平均逃避潜伏期比假手术组长，直线式和趋向式比例比假手术组低，且海马神经元排列不规则乱，胞质深染；(2)模型组大鼠海马活性氧、丙二醛水平增加，超氧化物歧化酶活性降低；(3)番茄红素(50，100和200 mg/kg)干预均改善了上述变化，以番茄红素100 mg/kg组改善效果最显著；(4)假手术组和番茄红素100 mg/kg组大鼠海马结构中NRSF蛋白表达与模型组相比均降低；(5)上述数据证实，100 mg/kg番茄红素能较好地保护血管性痴呆大鼠的学习记忆功能，其保护作用是通过抑制海马氧化应激来实现。实验于2016-06经中国福建医科大学动物伦理委员会批准，批准号为2014-025。

orcid: 0000-0002-5546-9151 (Xiao-Zhen Zhao)

关键词: 血管性痴呆, 番茄红素, 神经元限制性沉默因子, 活性氧簇, 超氧化物歧化酶, 丙二醛, 双侧劲总动脉结扎, 学习记忆, 海马, 神经元, 神经再生

Abstract: Oxidative stress is involved in the pathogenesis of vascular dementia. Studies have shown that lycopene can significantly inhibit oxidative stress; therefore, we hypothesized that lycopene can reduce the level of oxidative stress in vascular dementia. A vascular dementia model was established by permanent bilateral ligation of common carotid arteries. The dosage groups were treated with lycopene (50, 100 and 200 mg/kg) every other day for 2 months. Rats without bilateral carotid artery ligation were prepared as a sham group. To test the ability of learning and memory, the Morris water maze was used to detect the average escape latency and the change of search strategy. Hematoxylin- eosin staining was used to observe changes of hippocampal neurons. The levels of oxidative stress factors, superoxide dismutase and malondialdehyde, were measured in the hippocampus by biochemical detection. The levels of reactive oxygen species in the hippocampus were observed by dihydroethidium staining. The distribution and expression of oxidative stress related protein, neuron-restrictive silencer factor, in hippocampal neurons were detected by immunofluorescence histochemistry and western blot assays. After 2 months of drug administration, (1) in the model group, the average escape latency was longer than that of the sham group, and the proportion of straight and tend tactics was lower than that of the sham group, and the hippocampal neurons were irregularly arranged and the cytoplasm was hyperchromatic. (2) The levels of reactive oxygen species and malondialdehyde in the hippocampus of the model group rats were increased, and the activity of superoxide dismutase was decreased. (3) Lycopene (50, 100 and 200 mg/kg) intervention improved the above changes, and the lycopene 100 mg/kg group showed the most significant improvement effect. (4) Neuron-restrictive silencer factor expression in the hippocampus was lower in the sham group and the lycopene 100 mg/kg group than in the model group. (5) The above data indicate that lycopene 100 mg/kg could protect against the learning-memory ability impairment of vascular dementia rats. The protective mechanism was achieved by inhibiting oxidative stress in the hippocampus. The experiment was approved by the Animal Ethics Committee of Fujian Medical University, China (approval No. 2014-025) in June 2014.

Key words: bilateral carotid artery ligation, lycopene, hippocampus, learning and memory, malondialdehyde, neuron, neuron-restrictive silencer factor, reactive oxygen species, superoxide dismutase