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二甲双胍改善大鼠青春期至成年期慢性乙醇摄入引起的记忆障碍:氧化应激和神经炎症的作用。

Metformin improved memory impairment caused by chronic ethanol consumption during adolescent to adult period of rats: Role of oxidative stress and neuroinflammation.

机构信息

Student Research Committee, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran; Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran; Departments of Physiology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.

Tropical and Communicable Diseases Research Centre, Iranshahr University of Medical Sciences, Iranshahr, Iran.

出版信息

Behav Brain Res. 2021 Aug 6;411:113399. doi: 10.1016/j.bbr.2021.113399. Epub 2021 Jun 1.

Abstract

OBJECTIVE

Adolescence is a crucial time for brain maturation. We investigated the protective effects of metformin (Met) on behavioral changes, oxidative stress, tumor necrosis factor alpha (TNF-α) and nitrite in adulthood induced by ethanol (Eth) consumption during adolescent to adult period of rats.

MATERIALS AND METHODS

The adolescence male rats (21 days old) were treated as: 1) Control, 2) Eth (Eth in drinking water (20 %)), 3-5) Eth-Met50, 100 and 150 mg/kg (Eth in drinking water and Met (50, 100, or 150 mg/kg). After 5 weeks treatment, Morris water maze (MMW) and passive avoidance (PA) tests were done.

RESULTS

The latency in the MWM test was higher and the latency to enter the dark chamber in the PA test was lower in the Eth group than in control. In Eth-Met100 and 150 groups, they were less than the Eth group. Malondialdehyde (MDA) and nitrite concentration in the hippocampus and cortex of the Eth group were higher than the control group. The thiol content and catalase and superoxide dismutase (SOD) activities in hippocampal and cortical tissues of the Eth group reduced compared to the control group. TNF-α was higher in hippocampal tissues of Eth group animals. Met reversed all of these effects.

CONCLUSION

Our findings showed that the protective effects of Met against chronic Eth consumption induced learning and memory impairment were accompanied by decreasing of TNF-a, nitrite and oxidative stress in adolescent rats.

摘要

目的

青春期是大脑成熟的关键时期。我们研究了二甲双胍(Met)对雄性青春期至成年期持续摄入乙醇(Eth)诱导的成年期行为改变、氧化应激、肿瘤坏死因子-α(TNF-α)和亚硝酸盐的保护作用。

材料和方法

青春期雄性大鼠(21 天龄)处理如下:1)对照组,2)Eth 组(饮用水中含有 20%的 Eth),3-5)Eth-Met50、100 和 150mg/kg 组(饮用水中含有 Eth 和 50、100 或 150mg/kg 的 Met)。经过 5 周的治疗后,进行 Morris 水迷宫(MMW)和被动回避(PA)测试。

结果

Eth 组在 MMW 测试中的潜伏期较高,在 PA 测试中进入暗室的潜伏期较低。与 Eth 组相比,Eth-Met100 和 150 组的潜伏期较短。Eth 组海马和皮质中的丙二醛(MDA)和亚硝酸盐浓度高于对照组。与对照组相比,Eth 组海马和皮质组织中的巯基含量以及过氧化氢酶和超氧化物歧化酶(SOD)活性降低。Eth 组海马组织中的 TNF-α水平升高。Met 逆转了所有这些效应。

结论

我们的研究结果表明,Met 对慢性 Eth 摄入诱导的学习和记忆障碍具有保护作用,其机制可能与降低 TNF-α、亚硝酸盐和氧化应激有关。

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