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N-乙酰半胱氨酸对 MK-801 诱导的小鼠神经退行性变的保护作用。

The protective effect of N-acetylcysteine against MK-801-induced neurodegeneration in mice.

机构信息

Department of Anatomy, Faculty of Veterinary Medicine, Afyon Kocatepe University, Afyon, 03200, Turkey.

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Afyon Kocatepe University, Afyon, 03200, Turkey.

出版信息

Mol Biol Rep. 2023 Dec;50(12):10287-10299. doi: 10.1007/s11033-023-08881-9. Epub 2023 Nov 16.

Abstract

BACKGROUND

Neurological disorders result in not only a decline in the quality of life of patients but also a global economic burden. Therefore, protective medicine becomes more important for society. MK-801 is a chemical agent used to understand the etiology of behavioral disorders and brain degeneration in animal models. This study aims to determine whether N-acetylcysteine (NAC) is useful to treat brain degeneration caused by MK-801, an N-methyl-D-aspartate glutamate receptor antagonist.

METHODS AND RESULTS

Four groups were formed by dividing 24 male BALB/c mice into groups of six. The control group was given a saline solution (10 ml/kg-i.p.). MK-801 (1 mg/kg-i.p.) was given alone to one group, and it was given with NAC (100 mg/kg-i.p.) to another group, while the last group was given only NAC (100 mg/kg-i.p.). The administration of drugs lasted for fourteen days. After the behavioral tests (open field and elevated plus-maze), all animals were euthanised, and brain tissues were collected for real-time PCR, TAS-TOS analysis, hematoxylin-eosin, Kluver-Barrera, and TUNEL staining. In the MK-801 group, besides nuclear shrinkage in neurons, glial cell infiltration, vacuolization in cortical neurons, white matter damage, and apoptosis were observed.

CONCLUSION

In the mice given NAC as a protective agent, it was observed that behavioral problems improved, antioxidant levels increased, and nuclear shrinkage, glial cell infiltration, vacuolization in neurons, and white matter degeneration were prevented. Moreover, MBP expression increased, and the number of TUNEL-positive cells significantly decreased. As a result, it was observed that NAC may have a protective effect against brain degeneration.

摘要

背景

神经紊乱不仅导致患者生活质量下降,还给全球带来经济负担。因此,保护医学对社会变得更加重要。MK-801 是一种化学试剂,用于在动物模型中了解行为障碍和大脑退化的病因。本研究旨在确定 N-乙酰半胱氨酸(NAC)是否对治疗 MK-801(一种 N-甲基-D-天冬氨酸谷氨酸受体拮抗剂)引起的大脑退化有用。

方法和结果

将 24 只雄性 BALB/c 小鼠分为 6 组,每组 6 只。对照组给予生理盐水(10 ml/kg-i.p.)。一组给予 MK-801(1 mg/kg-i.p.),另一组给予 NAC(100 mg/kg-i.p.),另一组仅给予 NAC(100 mg/kg-i.p.)。药物治疗持续 14 天。行为测试(旷场和高架十字迷宫)后,处死所有动物,收集脑组织进行实时 PCR、TAS-TOS 分析、苏木精-伊红、Klüver-Barrera 和 TUNEL 染色。在 MK-801 组中,除了神经元核收缩外,还观察到神经胶质细胞浸润、皮质神经元空泡化、白质损伤和细胞凋亡。

结论

在给予 NAC 作为保护剂的小鼠中,观察到行为问题得到改善,抗氧化水平升高,核收缩、神经胶质细胞浸润、神经元空泡化和白质退化得到预防。此外,MBP 表达增加,TUNEL 阳性细胞数量显著减少。结果表明,NAC 可能对大脑退化具有保护作用。

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