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西普洛芬通过调节小鼠大脑中的胆碱能传递来减轻脂多糖引起的记忆障碍。

Ciproxifan attenuates the memory impairment induced by lipopolysaccharide through modulation of cholinergic transmission in the mouse brain.

机构信息

Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah, Kingdom of Saudi Arabia.

出版信息

Eur Rev Med Pharmacol Sci. 2022 Mar;26(6):1897-1905. doi: 10.26355/eurrev_202203_28335.

Abstract

OBJECTIVE

We investigated the protective effect of ciproxifan on lipopolysaccharide (LPS)-induced memory impairment by altering the cholinergic system in a mouse model.

MATERIALS AND METHODS

Groups of mice were given ciproxifan (1 or 3 mg/kg, p.o.) for 30 days. Neurotoxicity was induced with four doses of LPS (250 µg/kg, i.p.) from day-22 to day-25 of drug treatment in three groups. Then, mice were subjected to behavioral assessments using tests [elevated plus maze (EPM), novel object recognition (NOR), and Y-maze]. Also, brain tissues were collected for estimation of cholinergic transmission [acetylcholine (ACh) and acetylcholinesterase (AChE) levels].

RESULTS

Ciproxifan could rescue the memory impairment caused by LPS by shortening the transfer latency in the EPM test, increasing the time spent to explore a novel object and increasing the Discrimination Index in the NOR test and increasing the number of entries to the novel arm and duration of time spent in the novel arm in the Y-maze test. Ciproxifan increased the levels of ACh by decreasing AChE activity in LPS-treated mice.

CONCLUSIONS

Ciproxifan treatment can improve memory impairment in mice by increasing ACh levels and decreasing AChE levels.

摘要

目的

通过改变胆碱能系统,我们研究了西普福尼对脂多糖(LPS)诱导的记忆障碍的保护作用,建立了一个小鼠模型。

材料和方法

将小鼠分为几组,每天给予西普福尼(1 或 3mg/kg,po)30 天。在药物治疗的第 22 天至第 25 天,三组小鼠分别接受四剂 LPS(250μg/kg,ip)诱导神经毒性。然后,通过[高架十字迷宫(EPM)、新物体识别(NOR)和 Y 迷宫]测试对小鼠进行行为评估。此外,还收集脑组织以评估胆碱能传递[乙酰胆碱(ACh)和乙酰胆碱酯酶(AChE)水平]。

结果

西普福尼可通过缩短 EPM 测试中的转移潜伏期、增加探索新物体的时间、增加 NOR 测试中的辨别指数以及增加 Y 迷宫测试中进入新臂的次数和在新臂中花费的时间,来挽救 LPS 引起的记忆障碍。西普福尼通过降低 LPS 处理小鼠的 AChE 活性来增加 ACh 水平。

结论

西普福尼治疗可通过增加 ACh 水平和降低 AChE 水平来改善 LPS 处理小鼠的记忆障碍。

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