Role of ERK signaling pathway in morphine-or sufentanil-induced inhibition of arrhythmia induced by myocardial ischemia-reperfusion in rats: the relationship with Cx43 expression / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of extracellular signal-regulated kinase (ERK) signaling pathway in morphine-or sufentanil-induced inhibition of arrhythmia induced by myocardial ischemia-reperfusion (I/R) in rats and the relationship with connexin43 (Cx43).Methods Forty-eight healthy SPF adult male Sprague-Dawley rats,weighing 200-300 g,were randomly divided into 6 groups (n=8 each) using a random number tablesham operation group (group S);I/R group;morphine group (group M);sufentanil group (group Suf);morphine + ERK inhibitor PD98059 group (group MP);sufentanil + PD98059 group (group SP).Myocardial ischemia was induced by 30 min occlusion of the left anterior descending branch of the coronary artery,followed by reperfusion.In M and Suf groups,the animals were subjected to three cycles of 5-minute drug infusion (morphine 0.3 mg/kg and sufentanil 3 μg/kg,respectively) via the femoral vein interspersed with 5-minute drug-free periods starting from the time point immediately before ischemia.PD98059 10 mg/kg was injected intravenously at 10 min before ischemia in MP and SP groups.The development of ventricular arrhythmia was recorded within 30 min of ischemia and 30 min of reperfusion,and the arrhythmia was scored (AS).The animals were then sacrificed at 120 min of reperfusion,and the myocardial specimens were obtained for determination of the expression of total Cx43 (t-Cx43),phosphorylated Cx43 (p-Cx43),and phosphorylated ERK (p-ERK) by Western blot.Results Compared with group S,the AS was significantly increased,and the expression of p-Cx43 was significantly down-regulated in the other groups,and the expression of t-Cx43 and p-ERK was significantly down-regulated in I/R,SP and MP groups (P＜0.05).Compared with group I/R,the AS was significantly decreased,and the expression of t-Cx43,p-Cx43 and p-ERK was significantly up-regulated in M and Suf groups (P ＜ 0.05).Compared with M and Suf groups,the AS was significantly increased,and the expression of t-Cx43 and p-Cx43 was significantly down-regulated in SP and MP groups (P ＜ 0.05).Conclusion The mechanism by which morphine or sufentanil inhibits arrhythmia induced by myocardial I/R is associated with up-regulated expression of myocardial Cx43 after activation of ERK signaling pathway in rats.