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橙皮苷对氯化铝诱导的Wistar大鼠阿尔茨海默病的神经保护作用。

Neuroprotective effect of hesperidin on aluminium chloride induced Alzheimer's disease in Wistar rats.

作者信息

Justin Thenmozhi Arokiasamy, Raja Tharsius Raja William, Janakiraman Udaiyappan, Manivasagam Thamilarasan

机构信息

Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar, 608 002, Tamil Nadu, India,

出版信息

Neurochem Res. 2015 Apr;40(4):767-76. doi: 10.1007/s11064-015-1525-1. Epub 2015 Jan 29.

DOI:10.1007/s11064-015-1525-1
PMID:25630717
Abstract

The present study was aimed to evaluate the protective effect of hesperidin (Hes) on aluminium chloride (AlCl3) induced neurobehavioral and pathological changes in Alzheimeric rats. Intraperitonial injection of AlCl3 (100 mg/kg body weight) for 60 days significantly elevated the levels of aluminium (Al), activity of acetylcholinesterase (AChE) and protein expressions of amyloid precursor protein (APP), β amyloid (Aβ 1-42), β and γ secretases as compared to control group in hippocampus and cortex of rat brain. Hes administration orally along with AlCl3 injection for 60 days, significantly revert the Al concentration, AChE activity and Aβ synthesis-related molecules in the studied brain regions. Our results showed that aluminum exposure was significantly reduced the spontaneous locomotor and exploratory activities in open field test and enhanced the learning and memory impairments in morris water maze test. The behavioral impairments caused by aluminum were significantly attenuated by Hes. The histopathological studies in the hippocampus and cortex of rat brain also supported that Hes (100 mg/kg) markedly reduced the toxicity of AlCl3 and preserved the normal histoarchitecture pattern of the hippocampus and cortex. From these results, it is concluded that hesperidin can reverse memory loss caused by aluminum intoxication through attenuating AChE activity and amyloidogenic pathway.

摘要

本研究旨在评估橙皮苷(Hes)对氯化铝(AlCl3)诱导的阿尔茨海默病大鼠神经行为和病理变化的保护作用。与对照组相比,腹腔注射AlCl3(100 mg/kg体重)60天显著提高了大鼠脑海马和皮质中铝(Al)的水平、乙酰胆碱酯酶(AChE)的活性以及淀粉样前体蛋白(APP)、β淀粉样蛋白(Aβ 1-42)、β和γ分泌酶的蛋白表达。与AlCl3注射同时口服给予Hes 60天,可显著逆转所研究脑区中的铝浓度、AChE活性以及与Aβ合成相关的分子水平。我们的结果表明,铝暴露显著降低了旷场试验中的自发运动和探索活动,并加重了莫里斯水迷宫试验中的学习和记忆障碍。铝引起的行为障碍被Hes显著减轻。大鼠脑海马和皮质的组织病理学研究也支持,Hes(100 mg/kg)显著降低了AlCl3的毒性,并保留了海马和皮质的正常组织结构模式。从这些结果可以得出结论,橙皮苷可通过减弱AChE活性和淀粉样蛋白生成途径来逆转铝中毒引起的记忆丧失。

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