κ-opioid receptor agonist U50, 488H attenuates myocardial ischemia-reperfusionvia modulating Toll-like receptor 4/nuclear factor-κB signaling in rat.
- Author:
Wenke CAI
1
;
Yan ZHANG
2
;
Jiguo LI
;
Jian WANG
Author Information
- Publication Type:Journal Article
- MeSH: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; pharmacology; Animals; Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Coronary Artery Disease; Down-Regulation; Heart Conduction System; abnormalities; Myocardial Infarction; Myocardial Ischemia; metabolism; Myocardium; NF-kappa B; Naltrexone; analogs & derivatives; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; physiology; Reperfusion Injury; Signal Transduction; Toll-Like Receptor 4; physiology; Tumor Necrosis Factor-alpha
- From: Chinese Journal of Cardiology 2014;42(10):866-872
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo observe the effects of κ-opioid receptor agonist U50, 488H on myocardial ischemia and reperfusion injury and related mechanism.
METHODSRats were randomly divided into sham operation, myocardial ischemia and reperfusion(I/R, 30 min ischemia followed by 120 min reperfusion), and MI/R+U50, 488H (1.5 mg/kg) and I/R+U50, 488H+ selective κ-opioid receptor antagonist Nor-BNI (2 mg/kg, n = 8 each). The infarction size and the incidence of ventricular arrhythmias were observed.Real-time PCR and DAB staining were used to define the myocardium Toll-like receptor 4(TLR4) expression. Myeloperoxidase level, TNF-α induction and the expression of NF-κB were also examined in rats.
RESULTSAfter I/R, the expressions of myocardial TLR4 and NF-κB increased significantly both in ischemia area and area at risk. Compared with I/R, κ-opioid receptor stimulation with U50, 488H significantly attenuated the expressions of TLR4 and NF-κB and reduced myeloperoxidase (MPO) levels, myocardial TNF-α production, myocardial infarct sizes and the incidence of ventricular arrhythmias and arrhythmia score (2.9 ± 0.7 vs. 4.4 ± 0.9, P < 0.05) , above effects of U50, 488H were partly abolished by co-treatment with Nor-BNI.
CONCLUSIONThese data provide evidence for the first time that κ-opioid receptor stimulation could attenuate myocardial I/R injury via downregulating TLR4/NF-κB signaling in rats.
