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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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

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	CHEN Hong
	LIANG Yan
	JIN Yingli
	YU Xichong
	ZHAO Yongzhong
	WANG Weiqian
	LIN Qingxia
	LIN Haixi
	YANG Chuang

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

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