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苦参碱通过抑制 AChE/BuChE 和氧化应激对东莨菪碱诱导的记忆障碍的神经保护作用。

Neuroprotective effects of matrine on scopolamine-induced amnesia via inhibition of AChE/BuChE and oxidative stress.

机构信息

College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, People's Republic of China.

出版信息

Metab Brain Dis. 2019 Feb;34(1):173-181. doi: 10.1007/s11011-018-0335-y. Epub 2018 Nov 7.

Abstract

The present study was designed to evaluate the effects of matrine (MAT) on scopolamine (SCOP)-induced learning and memory impairment. After successive oral administration of MAT to mice for three days at doses of 0.4, 2, and 10 mg/kg, we assessed improvements in learning and memory and investigated the mechanism of action of SCOP-induced amnesia. Donepezil at a dose of 3 mg/kg was used as a standard memory enhancer. MAT significantly improved SCOP-induced learning and memory impairment in novel object recognition and Y-maze tests at doses of 0.4, 2, and 10 mg/kg. Furthermore, MAT inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and decreased oxidative stress in the brain, as evidenced by increased total antioxidant capacity, total superoxide dismutase levels, and catalase activities as well as decreased malondialdehyde levels. Additionally, there was a significant negative correlation between the percentage of spontaneous alternation in the Y maze and AChE activity in the cortex and hippocampus. MAT ameliorated SCOP-induced amnesia by the inhibition of both AChE/BuChE activities and oxidative stress. This study provides further evidence to encourage the development of MAT as a drug for the prevention or treatment of Alzheimer's disease.

摘要

本研究旨在评估苦参碱(MAT)对东莨菪碱(SCOP)诱导的学习和记忆障碍的影响。连续三天给小鼠口服不同剂量(0.4、2 和 10mg/kg)的 MAT 后,我们评估了学习和记忆的改善情况,并研究了 SCOP 诱导的遗忘的作用机制。多奈哌齐 3mg/kg 作为标准记忆增强剂。MAT 在新物体识别和 Y 迷宫试验中显著改善 SCOP 诱导的学习和记忆障碍,剂量为 0.4、2 和 10mg/kg。此外,MAT 抑制乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BuChE)活性,并降低大脑中的氧化应激,表现为总抗氧化能力、总超氧化物歧化酶水平和过氧化氢酶活性增加,以及丙二醛水平降低。此外,Y 迷宫中自发交替的百分比与皮质和海马中的 AChE 活性呈显著负相关。MAT 通过抑制 AChE/BuChE 活性和氧化应激改善 SCOP 诱导的遗忘。这项研究提供了进一步的证据,鼓励将 MAT 开发为预防或治疗阿尔茨海默病的药物。

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