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单酰甘油脂肪酶抑制剂 JZL-184 可在小鼠大脑中动脉闭塞性中风模型中发挥神经保护作用。

Monoacylglycerol lipase inhibitor, JZL-184, confers neuroprotection in the mice middle cerebral artery occlusion model of stroke.

机构信息

Department of Physiology and Pharmacology, School of Medicine, Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Student Research Committee, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

Department of Physiology and Pharmacology, School of Medicine, Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

出版信息

Life Sci. 2018 Apr 1;198:143-148. doi: 10.1016/j.lfs.2018.02.036. Epub 2018 Feb 27.

DOI:10.1016/j.lfs.2018.02.036
PMID:29496497
Abstract

INTRODUCTION

Investigators are searching to find new therapeutic strategies to reduce stroke secondary injury. JZL-184 (JZL) is an inhibitory factor for production of arachidonic acid (AA). Thus, it suppresses production of AA metabolites which are the cause of inflammation and tissue edema. Therefore, JZL may be considered for suppression of stroke secondary injury in mice middle cerebral artery occlusion (MCAO) model. Additionally, Aspirin is a known anti-inflammatory factor which is used to reduce pro-inflammatory secondary injury. The aim of this study was to determine the effects of JZL on the reduction of stroke secondary injury and to compare them with Aspirin effects.

MATERIAL AND METHODS

MCAO model has been induced and accordingly 83 male MCAO induced mice have been introduced to the study. The animals were divided to seven groups including intact, controls, vehicle, Aspirin, JZL 4, 8 and 16 mg/kg administrated groups. Brain edema and infarction, behavioral functions and brain levels of IL-10, TNF-α and matrix metaloperoteinase-9 (MMP9) have been examined in the evaluated groups.

RESULTS

The results revealed that JZL reduced brain edema, infarction, brain levels of TNF-α and MMP9 and also increased brain levels of IL-10 as well as improved behavioral functions in all three concentrations. The therapeutic effects of JZL were observed as well as Aspirin.

DISCUSSION

Based on the results, it seems that JZL can be considered as a good candidate for inhibition of stroke secondary injury in the case of delayed treatment.

摘要

简介

研究人员正在寻找新的治疗策略来减轻中风的继发性损伤。JZL-184(JZL)是一种抑制花生四烯酸(AA)生成的抑制剂。因此,它抑制了AA 代谢物的产生,AA 代谢物是炎症和组织水肿的原因。因此,JZL 可能被认为可用于抑制小鼠大脑中动脉闭塞(MCAO)模型中的中风继发性损伤。此外,阿司匹林是一种已知的抗炎因子,用于减轻促炎的继发性损伤。本研究的目的是确定 JZL 对减少中风继发性损伤的影响,并将其与阿司匹林的效果进行比较。

材料和方法

MCAO 模型已被诱导,相应地将 83 只雄性 MCAO 诱导的小鼠引入研究。动物被分为七组,包括完整组、对照组、载体组、阿司匹林组、JZL4、8 和 16mg/kg 给药组。评估组检查了脑水肿和梗死、行为功能以及脑内 IL-10、TNF-α 和基质金属蛋白酶-9(MMP9)的水平。

结果

结果表明,JZL 可降低脑水肿、梗死、脑 TNF-α 和 MMP9 水平,并增加脑 IL-10 水平,改善三种浓度的行为功能。JZL 的治疗效果与阿司匹林一样明显。

讨论

基于结果,JZL 似乎可以被认为是延迟治疗中风继发性损伤的良好候选药物。

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