Objective To evaluate the role of nuclear factor erythroid 2-related factor 2/antioxidant responsive element (Nrt2/ARE) signaling pathway inthe reduction of myocardial ischemia-reperfusion (I/R) injury by propofol in rats.Methods Sixty adult male Sprague-Dawley rats,weighing 200-240 g,were randomly divided into 5 groups (n =12 each) using a random number table:sham operation group (S group),I/R group,propofol group (P group),propofol + Nrf2 vehicle-plasmid group (PNV group) and propofol + Nrf2 siRNA plasmid group (PNS group).The animals were anesthetized with inhalation of 2％ isoflurane,tracheally intubated and mechanically ventilated.Myocardial I/R was produced by 5 min occlusion of left anterior descending branch of coronary artery followed by 60 min reperfusion.In P,PNV and PNS groups,isoflurane inhalation was stopped after successful intubation and propofol was infused via the caudal vein at 6 mg· kg-1 · h-1 until 30 of reperfusion.At 30 min of propofol infusion,Nrf2 vehicle-plasmid 10 μg (100 μl) was injected intramyocardially before myocardial ischemia in group PNV,and Nrf2 siRNA 10 μg (100 μl) was injected intramyocardially before myocardial ischemia in group PNS.The animals were sacrificed at 60 min of reperfusion and myocardial specimens were taken for determination of the infarct size,apoptosis index,and the expression of Nrf2 and heme oxygenase-1 (HO-1).Results Compared with group S,the infarct size and apoptosis index were significantly increased,and the expression of Nrf2 and HO-1 was up-regulated in I/R and P groups.Compared with group I/R,the infarct size and apoptosis index were significantly decreased,and the expression of Nrf2 and HO-1 was up-regulated in group P.Compared with group P,no significant changes were found in the infarct size,apoptosis index and expression of Nrf2 and HO-1 in group PNV,and the infarct size and apoptosis index were significantly increased,and the expression of Nrf2 and HO-1 was down-regulated in group PNS.Conclusion Nrf2/ARE signaling pathway is involved in the reduction of myocardial I/R injury by propofol in rats.