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丙酮酸乙酯通过维持认知功能、降低氧化应激、半胱天冬酶3激活和白细胞介素-1β水平来预防慢性脑灌注不足。

Ethyl pyruvate prevents from chronic cerebral hypoperfusion via preserving cognitive function and decreasing oxidative stress, caspase 3 activation and IL-1β level.

作者信息

Ozacmak H Sayan, Ozacmak V H, Turan I

出版信息

Bratisl Lek Listy. 2018;119(8):469-475. doi: 10.4149/BLL_2018_086.

DOI:10.4149/BLL_2018_086
PMID:30160153
Abstract

BACKGROUND

One of the important risk factors for dementia is chronic cerebral hypoperfusion (CCH) especially in patients with cerebrovascular disease.

OBJECTIVES

In the present study, using rat model of bilateral common carotid artery occlusion, the possible protective effects of ethyl pyruvate (EP) have been explored in terms of memory impairment, oxidative stress, and levels of caspase-3, Na-K ATPase, and IL- 1β.

METHODS

Rats were treated with EP (50 mg/kg, i.p) for 4 weeks. Cognitive function was evaluated by Morris Water Maze (MWM). Both levels of caspase-3 and Na-K ATPase in tissue, IL-1β in plasma were measured by ELISA method. Status of oxidative stress in brain was assessed by the measurements of the tissue malondialdehyde (MDA) and reduced glutathione (GSH) contents.  RESULTS: Results showed that CCH caused a striking impairment of spatial working memory, accompanied with increased levels of MDA and IL-1β as well as caspase 3 level. The treatment with EP, however, significantly improved the memory impairment. Moreover, the treatment also provided beneficial effects on the disturbances of caspase 3, IL-1β and MDA.

CONCLUSION

This study strongly imply that the EP administration can alleviate the memory impairment observed due to CCH. The protection provided by EP may result from inhibition of inflammatory response, apoptotic processes and oxidative stress (Fig. 3, Ref. 58).

摘要

背景

痴呆的重要危险因素之一是慢性脑灌注不足(CCH),尤其是在脑血管疾病患者中。

目的

在本研究中,使用双侧颈总动脉闭塞大鼠模型,从记忆障碍、氧化应激以及半胱天冬酶-3、钠钾ATP酶和白细胞介素-1β水平方面探讨丙酮酸乙酯(EP)可能的保护作用。

方法

大鼠用EP(50mg/kg,腹腔注射)治疗4周。通过莫里斯水迷宫(MWM)评估认知功能。采用酶联免疫吸附测定(ELISA)法测量组织中半胱天冬酶-3和钠钾ATP酶水平以及血浆中白细胞介素-1β水平。通过测量组织丙二醛(MDA)和还原型谷胱甘肽(GSH)含量评估脑内氧化应激状态。

结果

结果显示,CCH导致空间工作记忆显著受损,同时MDA、白细胞介素-1β水平以及半胱天冬酶3水平升高。然而,EP治疗显著改善了记忆障碍。此外,该治疗对半胱天冬酶3、白细胞介素-1β和MDA的紊乱也有有益作用。

结论

本研究强烈表明,给予EP可减轻因CCH所致的记忆障碍。EP提供的保护作用可能源于对炎症反应、凋亡过程和氧化应激的抑制(图3,参考文献58)。

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