Cardioprotective effects of combined therapy with diltiazem and superoxide dismutase on myocardial ischemia-reperfusion injury in rats
Cardioprotective effects of combined therapy with diltiazem and superoxide dismutase on myocardial ischemia-reperfusion injury in rats
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地尔硫卓与超氧化物歧化酶联合治疗对大鼠心肌缺血再灌注损伤的心脏保护作用
DOI：
10.1016/j.lfs.2017.06.024
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发表时间：
2017-08-15
期刊：
影响因子：
6.1
通讯作者：
Wu, Yinxiong
中科院分区：
文献类型：
--
作者：
Chen, Chunxia;Lu, Wensheng;Wu, Yinxiong
目的：本实验旨在研究地尔硫卓（DIL）联合超氧化物歧化酶（SOD）对大鼠心肌缺血再灌注（MIRI）损伤的影响，主要方法：将50只大鼠随机分为假手术组、缺血再灌注组、DIL（5 mg/kg）组、SOD（10，000 U/kg）组和联合治疗组（DIL + SOD）。通过结扎冠状动脉左前降支30 min再灌注60 min诱导MIRI。通过血流动力学、生化指标、组织病理学和凋亡相关蛋白和基因表达来评价组合疗法的心脏保护作用。与IR组相比，联合治疗组心功能明显改善，心律失常明显减少，心肌梗死面积和心肌酶释放。此外，组合疗法保护了心肌细胞结构，并显着减轻了氧化应激，导致Bcl-2和腺嘌呤核苷酸转运蛋白-1表达上调，Bax、caspase-3和切割的caspase-3表达下调。意义：结果表明，DIL联合SOD对大鼠MIRI具有保护作用，这些作用可能归因于减少氧应激损伤、减弱钙超载和抑制细胞凋亡。(C)2017 Elsevier Inc版权所有。
Aims: Our experiments were designed to study the effect of diltiazem (DIL) combined with superoxide dismutase (SOD) on myocardial ischemia-reperfusion (MIRI) injury in a rat model.Main methods: Fifty rats were randomly separated into sham, ischemia-reperfusion (IR), DIL (5 mg/kg), SOD (10,000 U/kg) and combinatorial therapy (DIL plus SOD) groups. MIRI was induced by ligating the left anterior descending coronary artery for 30 min and then reperfusing for 60 min. The cardioprotective effects of combinatorial therapy were evaluated using hemodynamics, biochemical indices, histopathology and apoptotic-related proteins and gene expression.Key findings: Compared with the IR group, combinatorial therapy significantly improved cardiac function and decreased arrhythmia, myocardial infarction area and release of myocardial enzyme. In addition, combinatorial therapy protected the myocardial cell structure as well as markedly alleviated oxidative stress, resulting in upregulation of Bcl-2 and adenine nucleotide transporter-1 expression as well as downregulation of Bax, caspase-3 and cleaved caspase-3 expression.Significance: Our results indicated that DIL combined with SOD can provide protection against MIRI in rats, and these effects may be attributed to a reduction in oxygen stress damage, attenuation of calcium overload, and inhibition of cell apoptosis. (C) 2017 Elsevier Inc All rights reserved.