title: κ-Opioid receptor stimulation modulates TLR4/NF-κB signaling in the rat heart subjected to ischemia-reperfusion.
abstract: It is well documented that the Toll-like receptor 4 (TLR4)/NF-κB signaling mediates early inflammation during myocardial ischemia and reperfusion. Our previous study has demonstrated that κ-opioid receptor stimulation with U50,488H produces cardioprotective and anti-inflammatory effects. The aim of the present study was to investigate whether κ-opioid receptor stimulation could modulate the TLR4/NF-κB signaling and reduce neutrophil accumulation and TNF-α induction in an ischemia-reperfusion injured rat heart model. Rats were randomly exposed to sham operation, myocardial ischemia and reperfusion (MI/R), and MI/R+U50,488H in the absence or presence of Nor-BNI, a selective κ-opioid receptor antagonist. The results demonstrated that after MI/R, the expressions of myocardial TLR4 and NF-κB increased significantly both in ischemia area and risking area. Compared with MI/R, κ-opioid receptor stimulation with U50,488H significantly attenuated the expressions of TLR4 and NF-κB. At the mean time, it also reduced myeloperoxidase (MPO) levels, both serum and myocardial TNF-α production, myocardial infarct sizes (INF/AAR%) and myocardial apoptosis induced by MI/R, all the effects of U50,488H were abolished by Nor-BNI. These data provide evidence for the first time that κ-opioid receptor stimulation inhibits TLR4/NF-κB signaling in the rat heart subjected to MI/R.
authors: Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, 710032 Shaanxi Province, PR China.
authors: JiaJi
authors: J
authors: Lin
authors: HaiYan
authors: H
authors: Wang
authors: Juan
authors: J
authors: Li
authors: QianMei
authors: Q
authors: Wang
authors: ShuMiao
authors: S
authors: Zhang
authors: Na
authors: N
authors: Feng
authors: Rong
authors: R
authors: Fan
authors: JianMing
authors: J
authors: Pei
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016328:NF-kappa B; D017473:Receptors, Opioid, kappa; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer