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ω-3 鱼油脂肪乳预处理通过醛应激减轻大鼠心肌氧化损伤。

ω-3 fish oil fat emulsion preconditioning mitigates myocardial oxidative damage in rats through aldehydes stress.

机构信息

Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.

Department of Anesthesiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China.

出版信息

Biomed Pharmacother. 2019 Oct;118:109198. doi: 10.1016/j.biopha.2019.109198. Epub 2019 Jul 20.

DOI:10.1016/j.biopha.2019.109198
PMID:31336342
Abstract

ω-3 fish oil fat emulsions contain a considerable quantity of unsaturated carbon-carbon double bonds, which undergo lipid peroxidation to yield low-dose aldehydes. These aldehydes may stimulate the production of antioxidant enzymes, thereby mitigating myocardial oxidative damage. This study aims to (1) verify the cardioprotective effect of ω-3 fish oil fat emulsion in vivo and in vitro, and (2) determine whether aldehyde stress is a protective mechanism. For modeling purposes, we pretreated rats with 2 ml/kg of a 10% ω-3 fish oil fat emulsion for 5 days in order to generate a sufficient aldehyde stress response to trigger the production of antioxidant enzymes, and we obtained similar response with H9C2 cells that were pretreated with a 0.5% ω-3 fish oil fat emulsion for 24 h. ω-3 fish oil fat emulsion pretreatment in vivo reduced the myocardial infarct size, decreased the incidence of arrhythmias, and promoted the recovery of cardiac function after myocardial ischemia/reperfusion injury. Once the expression of nuclear factor E2-related factor 2 (Nrf2) was silenced in H9C2 cells, aldehydes no longer produced enough antioxidant enzymes to reverse the oxidative damage caused by tert-butyl hydroperoxide (TBHP). Our results demonstrated that ω-3 fish oil fat emulsion enhanced the inhibition of oxidation and production of free radicals, and alleviated myocardial oxidative injury via activation of the Nrf2 signaling pathway.

摘要

ω-3 鱼油脂肪乳含有相当数量的不饱和碳-碳双键,这些双键会发生脂质过氧化反应,生成低剂量的醛类。这些醛类可能会刺激抗氧化酶的产生,从而减轻心肌氧化损伤。本研究旨在:(1) 验证 ω-3 鱼油脂肪乳在体内和体外的心脏保护作用;(2) 确定醛应激是否是一种保护机制。为此,我们用 2ml/kg 的 10%ω-3 鱼油脂肪乳预处理大鼠 5 天,以产生足够的醛应激反应来触发抗氧化酶的产生,我们还对用 0.5%ω-3 鱼油脂肪乳预处理 24 小时的 H9C2 细胞进行了类似的处理。体内用 ω-3 鱼油脂肪乳预处理可减少心肌梗死面积、降低心律失常发生率,并促进心肌缺血/再灌注损伤后的心脏功能恢复。一旦 H9C2 细胞中核因子 E2 相关因子 2(Nrf2)的表达被沉默,醛类就无法产生足够的抗氧化酶来逆转叔丁基过氧化氢(TBHP)引起的氧化损伤。我们的结果表明,ω-3 鱼油脂肪乳通过激活 Nrf2 信号通路增强了对氧化和自由基产生的抑制作用,从而减轻了心肌氧化损伤。

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