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Attenuation of inflammatory response and reduction in infarct size by postconditioning are associated with downregulation of early growth response 1 during reperfusion in rat heart.
- Source :
-
Shock (Augusta, Ga.) [Shock] 2014 Apr; Vol. 41 (4), pp. 346-54. - Publication Year :
- 2014
-
Abstract
- Early growth response 1 (EGR-1) works as a master regulator that plays a key role in triggering inflammation-induced tissue injury after ischemia and reperfusion. This study tested the hypothesis that postconditioning (Postcon) or anti-inflammatory compound, curcumin, ameliorates inflammatory responses and further reduces infarct size by normalizing EGR-1 expression during reperfusion. In the control group, male Sprague-Dawley rats were subjected to 30-min ischemia and 180-min reperfusion. Postcon with four cycles of 10-s/10-s reperfusion/ischemia was applied at the onset of reperfusion. Curcumin (150 mg/kg per day) was fed 5 days before ischemia. Relative to the control, Postcon reduced expression of EGR-1 mRNA and protein, as further identified by less EGR-1 immunoreactivity in myocardial nuclei and microvessels during reperfusion. Along with EGR-1 downregulation, levels of plasma and myocardial tumor necrosis factor α and interleukin 6 (IL-6) were significantly decreased. Upregulated P-selectin and intercellular adhesion molecule 1 mRNA and protein as well as their immunoreactivity at area at risk myocardium were significantly attenuated. Neutrophil extravasation identified by myeloperoxidase immunohistochemical staining was inhibited. Infarct size, determined with triphenyltetrazolium chloride staining, was smaller in the Postcon group than that in the control. The protection achieved with pretreatment with curcumin was comparable to the benefits gained by Postcon in all end points measured. In H9C2 rat cardiomyoblast cell line, EGR-1 siRNA downregulated hydrogen peroxide-induced EGR-1 mRNA expression and subsequently reduced tumor necrosis factor α mRNA level. These results suggest that EGR-1 seems to play a critical role in myocardial reperfusion injury because downregulation of EGR-1 either by Postcon or the use of pharmacological intervention reduces infarct size, most likely through an inhibition of inflammation-mediated processes.
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Anti-Inflammatory Agents, Non-Steroidal therapeutic use
Curcumin pharmacology
Curcumin therapeutic use
Early Growth Response Protein 1 antagonists & inhibitors
Early Growth Response Protein 1 genetics
Inflammation Mediators metabolism
Intercellular Adhesion Molecule-1 metabolism
Interleukin-6 biosynthesis
Male
Myocardial Infarction metabolism
Myocardial Reperfusion Injury metabolism
Myocardial Reperfusion Injury pathology
Myocardium metabolism
P-Selectin metabolism
Peroxidase metabolism
RNA, Messenger genetics
RNA, Small Interfering genetics
Rats
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha biosynthesis
Down-Regulation drug effects
Early Growth Response Protein 1 biosynthesis
Ischemic Postconditioning methods
Myocardial Infarction pathology
Myocardial Reperfusion Injury prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1540-0514
- Volume :
- 41
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Shock (Augusta, Ga.)
- Publication Type :
- Academic Journal
- Accession number :
- 24365880
- Full Text :
- https://doi.org/10.1097/SHK.0000000000000112