title: [κ-opioid receptor agonist U50, 488H attenuates myocardial ischemia-reperfusionvia modulating Toll-like receptor 4/nuclear factor-κB signaling in rat].
abstract: OBJECTIVE
  To observe the effects of κ-opioid receptor agonist U50, 488H on myocardial ischemia and reperfusion injury and related mechanism.
  
  
  METHODS
  Rats 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.
  
  
  RESULTS
  After 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Email: caiwenke002@126.com.
authors.forename: Wenke
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Cardiovascular Surgery, Kunming General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu 650032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jiguo
authors.initials: J
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac; D053840:Brugada Syndrome; D000075224:Cardiac Conduction System Disease; D003324:Coronary Artery Disease; D015536:Down-Regulation; D006329:Heart Conduction System / Q000002:abnormalities; D009203:Myocardial Infarction; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium; D016328:NF-kappa B; D009271:Naltrexone / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000502:physiology*; D015427:Reperfusion Injury; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D016328:NF-kappa B; D017473:Receptors, Opioid, kappa; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer