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氯化锂对 D-半乳糖诱导的大鼠行为和记忆障碍、氧化应激及 5-羟色胺功能改变的改善作用。

Ameliorative effect of lithium chloride against d-galactose induced behavioral and memory impairment, oxidative stress and alteration in serotonin function in rats.

机构信息

Department of Biochemistry, Faculty of Science, Bahauddin Zakariya University, Multan, Pakistan.

Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.

出版信息

Pharmacol Rep. 2019 Oct;71(5):909-916. doi: 10.1016/j.pharep.2019.04.022. Epub 2019 May 1.

DOI:10.1016/j.pharep.2019.04.022
PMID:31426009
Abstract

BACKGROUND

Aging is a phenomenon that all living organisms surely face. d-galactose (D-gal) has been used to develop an aging model of brain. Lithium (Li) has been proposed to have neuroprotective properties in relation to several neurological disorders. The goal of the current studyis to evaluate the effect of Lithium Chloride (LiCl) on D-gal induced neurological disorders and oxidative stress.

METHODS

Rats were treated with D-gal at a dose of 300 mg/ml/kg and various doses of LiCl (20, 40 and 80 mg/ml/kg) for 14 days. After that behavioral analysis (Elevated plus maze (EPM); Light dark box test (LDT); Morris water maze (MWM); Forced swim test (FST)) were performed. Animals were decapitated after behavioral tests and brain samples were collected for biochemical (malondialdehyde (MDA); superoxide dismutase (SOD); catalase (CAT); glutathione peroxidase (GPx); acetylcholiesterase (AChE)) and neurochemical analysis (5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)).

RESULTS

The results showed that administration of LiCl at all doses ameliorates D-gal induced, decreased time spent in the open arm and light box in EPM and LDT respectively, increased immobility in FST, increased latency escape in MWM, increased MDA levels, decreased antioxidant enzyme, increased AChE activity and decreased 5-HT metabolism.

CONCLUSIONS

In conclusion, the present study indicated that D-gal induced anxiety/depression like symptoms and memory impairment were ameliorated by LiCl (at all doses) possibly via its antioxidant effects and normalizing 5-HT function.

摘要

背景

衰老 是所有生物体都必然面临的现象。D-半乳糖(D-gal)已被用于开发大脑衰老模型。锂(Li)已被提出在与几种神经退行性疾病有关的方面具有神经保护作用。本研究的目的是评估氯化锂(LiCl)对 D-半乳糖诱导的神经紊乱和氧化应激的影响。

方法

将大鼠用 300mg/ml/kg 的 D-gal 处理,并以不同剂量的 LiCl(20、40 和 80mg/ml/kg)处理 14 天。之后进行行为分析(高架十字迷宫(EPM);明暗箱测试(LDT);水迷宫(MWM);强迫游泳测试(FST))。行为测试后处死动物,采集脑样进行生化分析(丙二醛(MDA);超氧化物歧化酶(SOD);过氧化氢酶(CAT);谷胱甘肽过氧化物酶(GPx);乙酰胆碱酯酶(AChE))和神经化学分析(5-羟色胺(5-HT)和 5-羟吲哚乙酸(5-HIAA))。

结果

结果表明,所有剂量的 LiCl 给药均能改善 D-gal 诱导的行为,分别减少 EPM 和 LDT 中开放臂和光箱的时间,增加 FST 中的不动性,增加 MWM 中的潜伏期逃避,增加 MDA 水平,降低抗氧化酶,增加 AChE 活性,降低 5-HT 代谢。

结论

总之,本研究表明,LiCl(所有剂量)可改善 D-gal 诱导的焦虑/抑郁样症状和记忆障碍,可能通过其抗氧化作用和 5-HT 功能正常化。

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