Effects of lipoxin A4 administered at different time points on connexin-43 expression during myocardial ischemia-reperfusion in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effects of lipoxin A4 (LXA4) administered at different time points on the expression of connexin43 (Cx43) during myocardial ischemia-reperfusion (I/R) in rats.Methods Seventytwo healthy male Sprague-Dawley rats,weighing 200-250 g,wcre equally and randomly divided into 6 groupsgroups sham operation Ⅰ (group S1) and Ⅱ (group S2),groups myocardial I/R Ⅰ (group Ⅰ/R1) and Ⅱ (group I/R2),and groups LXA4 administered before chest opening (group LX1) and at 30 min of reperfusion (group LX2).Myocardial I/R was produced by 30 min occlusion of left anterior descending branch (LAD) of coronary artery followed by 120 min reperfusion.LXA4 100μg/kg was injected via femoral veins before chest opening and at 30 min of reperfusion in groups LX1 and group LX2,respectively.While normal saline 2 ml/kg was injected via the femoral vein at the corresponding time points in the other four groups.In groups S1 and S2,LAD was only threaded,but not ligated.Blood samples were taken from the femoral vein before chest opening and at 120 min of reperfusion for measurement of serum IL-8,TNF-α and cardiac troponin Ⅰ (cTnI) concentrations.The rats were then sacrificed after blood samples were taken at 120 min of reperfusion and hearts were removed for determination of Cx43 protein (by immunohistochemical SP method) and Cx43 mRNA expression (by real-time quantitative PCR),SOD activity and MDA content in myocardial tissues.The development of arrhythmia was observed from occlusion of LAD to 120 min of reperfusion.Duration of ventricular tachycardia (VTd) and ventricular fibrillation (VFd) was recorded.Scores of ventricular arrhythmias were calculated.Results The expression of Cx43 protein and mRNA was significantly down-regulated,and scores of ventricular arrhythmias,VTd,serum IL-8,TNF-α and cTnI concentrations,SOD activity and MDA content were increased in groups I/R1 and LX1 as compared with group S1,and in groups I/R2 and LX2 as compared with group S2 (P ＜ 0.05).The expression of Cx43 protein and mRNA was significantly up-regulated,SOD activity was increased,and scores of ventricular arrhythmias,VTd,VFd,serum IL-8,TNF-α and cTnI concentrations,and MDA content were decreased in group LX1 as compared with group I/R1,and in group LX2 as compared with group I/R2(P ＜ 0.05).The expression of Cx43 protein and mRNA was significantly lower,scores of ventricular arrhythmias,VTd and SOD activity were higher,and the serum IL-8,TNF-α and cTnI concentrations and MDA content were lower in group LX2 than in group LX1 (P ＜ 0.05).Conclusion LXA4 administered before myocardial ischemia and at 30 min of reperfusion can up-regulate the expression of Cx43 and reverse remodeling of Cx43,thus reducing myocardial I/R-induced arrhythmia in rats,and LXA4 administered before ischemia can provide better efficacy.