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通过乙酰胆碱酯酶测定和行为测试评估槲皮素预处理对泊洛沙姆-407诱导的高脂血症大鼠的神经保护作用。

Neuroprotective effects of pretreatment with quercetin as assessed by acetylcholinesterase assay and behavioral testing in poloxamer-407 induced hyperlipidemic rats.

作者信息

Braun Josiane B S, Ruchel Jader B, Adefegha Stephen A, Coelho Ana Paula V, Trelles Kelly B, Signor Cristiane, Rubin Maribel A, Oliveira Juliana S, Dornelles Guilherme L, de Andrade Cinthia M, Castilhos Lívia G, Leal Daniela B R

机构信息

Programa de-Pós Graduação em Ciências Biológicas: Bioquímica Toxicológica, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, 97105-900, Brazil.

Graduação em Ciências Biológicas Universidade Federal de Santa Maria, RS, 97105-900, Brazil.

出版信息

Biomed Pharmacother. 2017 Apr;88:1054-1063. doi: 10.1016/j.biopha.2017.01.134. Epub 2017 Feb 7.

Abstract

Hyperlipidemia is a group of disorders characterized by excessive lipids in the bloodstream. It is associated with the incidence of cardiovascular diseases and recognized as the most important factor underlying the occurrence of atherosclerosis. This study was conducted to investigate whether pretreatment with quercetin can protect against possible memory impairment and deterioration of the cholinergic system in hyperlipidemic rats. Animals were divided into ten groups (n=7): saline/control, saline/quercetin 5mg/kg, saline/quercetin 25mg/kg, saline/quercetin 50mg/kg, saline/simvastatin (0.04mg/kg), hyperlipidemia, hyperlipidemia/quercetin 5mg/kg, hyperlipidemia/quercetin 25mg/kg, hyperlipidemia/quercetin 50mg/kg and hyperlipidemia/simvastatin. The animals were pretreated with quercetin by oral gavage for a period of 30days and hyperlipidemia was subsequently induced by intraperitoneal administration of a single dose of 500mg/kg of poloxamer-407. Simvastatin was administered after the induction of hyperlipidemia. The results demonstrated that hyperlipidemic rats had memory impairment compared with the saline control group (P<0.001). However, pretreatment with quercetin and simvastatin treatment attenuated the damage caused by hyperlipidemia compared with the hyperlipidemic group (P<0.05). Acetylcholinesterase (AChE) activity in the cerebral hippocampus was significantly (P<0.001) reduced in the hyperlipidemic group compared with the control saline group. Pretreatment with quercetin and simvastatin treatment in the hyperlipidemic groups significantly (P<0.05) increased AChE activity compared with the hyperlipidemic group. Our results thus suggest that quercetin may prevent memory impairment, alter lipid metabolism, and modulate AChE activity in an experimental model of hyperlipidemia.

摘要

高脂血症是一组以血液中脂质过多为特征的病症。它与心血管疾病的发生率相关,并被认为是动脉粥样硬化发生的最重要因素。本研究旨在调查槲皮素预处理是否能预防高脂血症大鼠可能出现的记忆障碍和胆碱能系统退化。动物被分为十组(n = 7):生理盐水/对照组、生理盐水/5mg/kg槲皮素组、生理盐水/25mg/kg槲皮素组、生理盐水/50mg/kg槲皮素组、生理盐水/辛伐他汀(0.04mg/kg)组、高脂血症组、高脂血症/5mg/kg槲皮素组、高脂血症/25mg/kg槲皮素组、高脂血症/50mg/kg槲皮素组和高脂血症/辛伐他汀组。通过口服灌胃用槲皮素对动物进行预处理30天,随后通过腹腔注射单剂量500mg/kg泊洛沙姆-407诱导高脂血症。高脂血症诱导后给予辛伐他汀。结果表明,与生理盐水对照组相比,高脂血症大鼠存在记忆障碍(P<0.001)。然而,与高脂血症组相比,槲皮素预处理和辛伐他汀治疗减轻了高脂血症造成的损害(P<0.05)。与生理盐水对照组相比,高脂血症组大脑海马中的乙酰胆碱酯酶(AChE)活性显著降低(P<0.001)。与高脂血症组相比,高脂血症组中槲皮素预处理和辛伐他汀治疗显著提高了AChE活性(P<0.05)。因此,我们的结果表明,在高脂血症实验模型中,槲皮素可能预防记忆障碍、改变脂质代谢并调节AChE活性。

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