ANTI-APOPTOTIC AND ANTI-INFLAMMATORY EFFECTS OF HYDROGEN SULFIDE IN A RAT MODEL OF REGIONAL MYOCARDIAL I/R

被引：258

作者：

Sivarajah, Ahila

Collino, Massimo ^{[2
]}

Yasin, Mohammed

Benetti, Elisa ^{[2
]}

Gallicchio, Margherita ^{[2
]}

Mazzon, Emanuela ^{[3
]}

Cuzzocrea, Salvatore ^{[4
]}

Fantozzi, Roberto ^{[2
]}

Thiemermann, Christoph ^{[1
]}

机构：

[1] Queen Mary Univ London, William Harvey Res Inst, St Bartholomews & Royal London Sch Med & Dent, Ctr Translat Med, London, England

[2] Univ Turin, Dept Anat Pharmacol & Forens Med, Turin, Italy

[3] IRCCS Ctr Neurosci Bonino Pulejo, Messina, Italy

[4] Univ Messina, Sch Med, Dept Expt Med & Pharmacol, I-98100 Messina, Italy

来源：

SHOCK | 2009年 / 31卷 / 03期

基金：

英国医学研究理事会;

关键词：

Apoptosis; hydrogen sulfide; infarct size; inflammation and regional myocardial infarction; ACTIVATED PROTEIN-KINASE; DECREASES CARDIOMYOCYTE APOPTOSIS; ISCHEMIA-REPERFUSION INJURY; NF-KAPPA-B; OXIDATIVE STRESS; GENE-EXPRESSION; GASTROINTESTINAL-TRACT; POTASSIUM CHANNELS; INFARCT SIZE; P38;

D O I：

10.1097/SHK.0b013e318180ff89

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

Hydrogen sulfide (H2S) is a novel gaseous mediator produced by cystathionine-beta-synthase and cystathionine-gamma-lyase in the cardiovascular system, including the heart. Using a rat model of regional myocardial ischemia/reperfusion, we investigated the effects of an H2S donor (sodium hydrogen sulfide [NaHS]) on the infarct size and apoptosis caused by ischemia (25 min) and reperfusion (2 h). Furthermore, we investigated the potential mechanism(s) of the cardioprotective effect(s) afforded by NaHS. Specifically, we demonstrate that NaHS (1) attenuates the increase in caspase 9 activity observed in cardiac myocytes isolated from the area at risk (AAR) of hearts subjected in vivo to regional myocardial I/R and (2) ameliorates the decrease in expression of Bcl-2 within the AAR obtained from rat hearts subjected to regional myocardial I/R. The cardioprotective effects of NaHS were abolished by 5-hydroxydeconoate, a putative mitochondrial adenosine triphosphate-sensitive potassium channel blocker. Furthermore, NaHS attenuated the increase in the I/R-induced (1) phosphorylation of p38 mitogen-activated protein kinase and Jun N-terminal kinase, (2) translocation from the cytosol to the nucleus of the p65 subunit of nuclear factor-kappa B, (3) intercellular adhesion molecule 1 expression, (4) polymorphonuclear leukocyte accumulation, (5) myeloperoxidase activity, (6) malondialdehyde levels, and (7) nitrotyrosine staining determined in the AAR obtained from rat hearts subjected to regional myocardial I/R. In conclusion, we demonstrate that the cardioprotective effect of NaHS is secondary to a combination of antiapoptotic and anti-inflammatory effects. The antiapoptotic effect of NaHS may be in part due to the opening of the putative mitochondrial adenosine triphosphate-sensitive potassium channels.

引用

页码：267 / 274

页数：8

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