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地尔硫䓬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

Cardioprotective effects of combined therapy with diltiazem and superoxide dismutase on myocardial ischemia-reperfusion injury in rats.

作者信息

Chen Chunxia, Lu Wensheng, Wu Guangwei, Lv Liwen, Chen Wan, Huang Luying, Wu Xubin, Xu Nengwen, Wu Yinxiong

机构信息

Department of Hyperbaric Oxygen, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, PR China.

Department of Endocrinology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, PR China.

出版信息

Life Sci. 2017 Aug 15;183:50-59. doi: 10.1016/j.lfs.2017.06.024. Epub 2017 Jun 27.

DOI:10.1016/j.lfs.2017.06.024
PMID:28666765
Abstract

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 (5mg/kg), SOD (10,000U/kg) and combinatorial therapy (DIL plus SOD) groups. MIRI was induced by ligating the left anterior descending coronary artery for 30min and then reperfusing for 60min. 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.

摘要

目的

我们的实验旨在研究地尔硫䓬(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(IR)组、DIL(5mg/kg)组、SOD(10000U/kg)组和联合治疗(DIL加SOD)组。通过结扎左冠状动脉前降支30分钟然后再灌注60分钟诱导MIRI。使用血流动力学、生化指标、组织病理学以及凋亡相关蛋白和基因表达来评估联合治疗的心脏保护作用。

主要发现

与IR组相比,联合治疗显著改善了心脏功能,降低了心律失常、心肌梗死面积和心肌酶释放。此外,联合治疗保护了心肌细胞结构,并明显减轻了氧化应激,导致Bcl-2和腺嘌呤核苷酸转运体-1表达上调,以及Bax、caspase-3和裂解的caspase-3表达下调。

意义

我们的结果表明,DIL联合SOD可以对大鼠MIRI提供保护,这些作用可能归因于氧应激损伤的减少、钙超载的减轻和细胞凋亡的抑制。

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