κ-opioid receptor agonist U50,488H attenuates myocardial ischemia-reperfusion via modulating Toll-like receptor 4/nuclear factor-κB signaling in rat
10.3760/cma.j.issn.0253-3758.2014.10.015
- VernacularTitle:κ阿片受体激动剂通过调控Toll样受体4/核因子-κB信号通路保护大鼠缺血再灌注心肌
- Author:
Wenke CAI
1
;
Yan ZHANG
;
Jiguo LI
;
Jian WANG
Author Information
1. 650032,成都军区昆明总医院心胸外科
- Keywords:
Myocardial reperfusion injury;
Receptors,opioid,kappa;
Toll-like receptor 4;
NF-kappa B
- From:
Chinese Journal of Cardiology
2014;42(10):866-872
- CountryChina
- Language:Chinese
-
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.Conclusion These data provide evidence for the first time that κ-opioid receptor stimulation could attenuate myocardial L/R injury via downregulating TLR4/NF-κB signaling in rats.
