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腺苷受体激活在离体大鼠心脏缺血再灌注期间抗氧化酶调节中的作用。

Role of adenosine receptor activation in antioxidant enzyme regulation during ischemia-reperfusion in the isolated rat heart.

作者信息

Hochhauser Edith, Kaminski Oleg, Shalom Hemdat, Leshem Dorit, Shneyvays Vladimir, Shainberg Asher, Vidne Bernardo A

机构信息

The Cardiac Research Laboratory of the Department of Cardiothoracic Surgery, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Rabin Medical Center, Petah Tikva, Israel.

出版信息

Antioxid Redox Signal. 2004 Apr;6(2):335-44. doi: 10.1089/152308604322899404.

Abstract

The aim of the present study was to investigate the protective role of pharmacological preconditioning on antioxidant enzymes using A(1) and A(3) adenosine receptor agonists in the recovery of the isolated myocardium after cardioplegic ischemia. Two different modes of preconditioning were studied: isolated rat hearts were perfused with A(1) receptor agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) or A(3) 2-chloro-N(6)-(3-iodobenzyl) adenosine-5'-N-methyluronamide (Cl-IB-MECA) (1 nM), followed by cardioplegic ischemia and reperfusion (30 min each) (perfusion mode), or CCPA or Cl-IB-MECA (100 micro g/kg) were injected intravenously 24 h before the experiment (injection mode). Hearts treated with CCPA improved in terms of mechanical function, infarct size, ATP levels, superoxide dismutase, and catalase (p < 0.005) in both modes of administration. Cl-IB-MECA was beneficial mainly in the injected group. Reduced damage to the mitochondria in the CCPA-treated hearts was observed using electron microscopy evaluation. In the Cl-IB-MECA-injected hearts, mitochondrial damage was moderate. CCPA in both modes of treatment and Cl-IB-MECA in the injected mode were beneficial in protecting the perfused isolated rat heart, subjected to normothermic cardioplegic ischemia. This protection was partially related to the higher myocardial activity of superoxide dismutase and catalase.

摘要

本研究旨在探讨使用A(1)和A(3)腺苷受体激动剂进行药理学预处理对抗氧化酶的保护作用,以及其在心脏停搏缺血后离体心肌恢复中的作用。研究了两种不同的预处理模式:用A(1)受体激动剂2-氯-N(6)-环戊基腺苷(CCPA)或A(3) 2-氯-N(6)-(3-碘苄基)腺苷-5'-N-甲基脲酰胺(Cl-IB-MECA)(1 nM)灌注离体大鼠心脏,随后进行心脏停搏缺血和再灌注(各30分钟)(灌注模式),或者在实验前24小时静脉注射CCPA或Cl-IB-MECA(100μg/kg)(注射模式)。在两种给药模式下,用CCPA处理的心脏在机械功能、梗死面积、ATP水平、超氧化物歧化酶和过氧化氢酶方面均有改善(p<0.005)。Cl-IB-MECA主要在注射组中有益。通过电子显微镜评估观察到,CCPA处理的心脏中线粒体损伤减少。在Cl-IB-MECA注射的心脏中,线粒体损伤为中度。两种治疗模式下的CCPA以及注射模式下的Cl-IB-MECA均有助于保护经历常温心脏停搏缺血的灌注离体大鼠心脏。这种保护作用部分与超氧化物歧化酶和过氧化氢酶较高的心肌活性有关。

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