Zhu Ning-Wei, Yin Xiao-Lan, Lin Ren, Fan Xiao-Lan, Chen Shi-Jie, Zhu Yuan-Ming, Zhao Xiao-Zhen
Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province; Department of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, Zhejiang Province, China.
Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province, China.
Neural Regen Res. 2020 Feb;15(2):332-341. doi: 10.4103/1673-5374.265565.
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.
氧化应激参与血管性痴呆的发病机制。研究表明，番茄红素可显著抑制氧化应激；因此，我们推测番茄红素可降低血管性痴呆中的氧化应激水平。通过永久性双侧结扎颈总动脉建立血管性痴呆模型。给药组每隔一天用番茄红素（50、100和200mg/kg）治疗2个月。将未进行双侧颈动脉结扎的大鼠作为假手术组。为测试学习和记忆能力，采用Morris水迷宫检测平均逃避潜伏期和搜索策略的变化。用苏木精-伊红染色观察海马神经元的变化。通过生化检测测定海马中氧化应激因子、超氧化物歧化酶和丙二醛的水平。用二氢乙锭染色观察海马中活性氧的水平。通过免疫荧光组织化学和蛋白质印迹分析检测海马神经元中氧化应激相关蛋白神经元限制性沉默因子的分布和表达。给药2个月后，（1）模型组的平均逃避潜伏期比假手术组长，直线和趋向策略的比例低于假手术组，海马神经元排列不规则且细胞质染色质增多。（2）模型组大鼠海马中活性氧和丙二醛水平升高，超氧化物歧化酶活性降低。（3）番茄红素（50、100和200mg/kg）干预改善了上述变化，其中100mg/kg番茄红素组的改善效果最显著。（4）假手术组和100mg/kg番茄红素组海马中神经元限制性沉默因子的表达低于模型组。（5）上述数据表明，100mg/kg番茄红素可预防血管性痴呆大鼠的学习记忆能力损害。其保护机制是通过抑制海马中的氧化应激实现的。本实验于2014年6月获得中国福建医科大学动物伦理委员会批准（批准号：2014-025）。
