褪黑素对精神分裂症模型大鼠海马神经元氧化应激损伤的保护作用

doi:10.3969/j.issn.2095-9400.2020.03.012

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摘要目的：研究褪黑素（MT）对精神分裂症模型大鼠海马神经元氧化应激损伤的保护作用及机制。方法：60只雄性SD大鼠被分为5组：对照组、模型组、模型+MT低剂量组（12.5 mg/kg）、模型+MT高剂量组（25 mg/kg）、模型+MT受体阻断剂组（Luzindole，1 mg/kg），每组12只。采用腹腔注射MK-801的方法建立精神分裂症大鼠模型，造模成功后，模型+MT低剂量组、模型+MT高剂量组以及模型+MT受体阻断剂组均腹腔注射相应药物，对照组及模型组注射10%无水乙醇溶液，持续21 d。采用Morris水迷宫实验检测大鼠的学习记忆功能，试剂盒法检测海马组织匀浆液中氧化应激相关因子ROS、SOD、MDA含量，免疫组织化学法检测神经元标记蛋白NeuN的表达，Western blot法检测海马核因子E2相关因子2（Nrf2）、血红素加氧酶-1（HO-1）蛋白水平。结果：与对照组比，模型组大鼠学习记忆功能受损，海马ROS、MDA含量显著增加，SOD活性下降，NeuN阳性细胞数明显减少，海马Nrf2、HO-1蛋白表达显著升高（均P＜0.05）；与模型组比，模型+MT高剂量组大鼠学习与记忆功能均有较明显的改善，海马ROS、MDA含量均下降，SOD活性升高，NeuN阳性表达增加，Nrf2、HO-1蛋白表达显著升高（均P＜0.01）。与模型+MT高剂量组比，模型+MT受体阻断剂组大鼠学习记忆功能受损，海马ROS含量上升，NeuN阳性表达下降，Nrf2、HO-1蛋白表达下降（P＜0.05）。结论：MT具有保护精神分裂症大鼠海马神经元氧化应激损伤的作用，其机制与调控Nrf2/HO-1信号通路有关。

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	陈宏
	梁艳
	金颖莉
	虞希冲
	赵永忠
	王维千
	林青霞
	林海西
	杨闯

关键词 ：褪黑素, 精神分裂症, 氧化应激, 海马, 核因子E2相关因子2/血红素加氧酶-1

Abstract：Objective: To study the protective effect of melatonin (MT) on oxidative stress injury and its mechanism in hippocampal neurons of schizophrenia model rats. Methods: Sixty male Sprague-Dawley rats were divided into 5 groups: control, model, model with low dose of MT (12.5 mg/kg), model with high dose of MT
(25 mg/kg), and model with MT receptor blocker (Luzindole, 1 mg/kg). Model of schizophrenia was established by intraperitoneal injection of MK-801. After successful modeling, the low- and high-dose of MT and MT receptor blocker groups were intraperitoneally injected with the corresponding drugs, and the control group and model group were injected with 10% absolute ethanol solution for 21 days. The learning and memory ability of SD rats was detected by Morris water maze test. The content of oxidative stress related factors ROS, SOD and MDA in hippocampal tissue homogenate was detected by kit. The expression of neuron marker protein NeuN was detected by immunohistochemistry and Western-blot was used to detect the levels of Nrf2 and HO-1 in hippocampus. Results: Compared with the control group, the model group was impaired in the learning and memory ability (P<0.05), the content of ROS and MDA in hippocampus was significantly increased (P<0.01), and the activity of SOD was decreased (P<0.05). The number of NeuN positive cells was significantly decreased (P<0.01), and the expression of Nrf2 and HO-1 protein in hippocampus was significantly increased (P<0.01). Compared with the model group, the high-dose MT group was significantly improved in the learning and memory ability (P<0.05), the hippocampal ROS and MDA content decreased and SOD increased (P<0.05). NeuN expression was increased (P<0.01), and Nrf2 and HO-1 protein expression was significantly increased (P<0.01). Administration of MT receptor blockers increased hippocampal ROS content in model rats (P<0.05) and mediated neuronal oxidative stress injury. Conclusion: Melatonin protects hippocampal neurons from oxidative stress in schizophrenia rats, and its mechanism is related to the regulation of Nrf2/HO-1 signaling pathway.

Key words： melatonin schizophrenia oxidative stress hippocampus Nrf2/HO-1

通讯作者: 杨闯，副主任医师，Email：dryangchuang@163.com。

作者简介: 陈宏（1976-），男，浙江瑞安人，主治医师，硕士。

链接本文:

https://xb.wmu.edu.cn/CN/10.3969/j.issn.2095-9400.2020.03.012 或 https://xb.wmu.edu.cn/CN/Y2020/V50/I3/227

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