Role of Nrf2/ARE signaling pathway in propofol-induced reduction of lung ischemia-reperfusion injury in aged rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway in propofol-induced reduction of lung ischemia-reperfusion (I/R) injury in aged rats.Methods Thirty-two clean healthy male Sprague-Dawley rats,aged 18-22 months,weighing 450-600,were divided into 4 groups (n =8 each) using a random number tablesham operation group (group S),I/R group (group I/R),I/R plus propofol group (group I/R+P) and all-trans retinoic acid (ARTA) plus I/R plus propofol group (group ARTA+I/R+P).Lung I/R was induced by occlusion of the right hilum of lung for 60 min followed by 120 min of reperfusion in anesthetized rats.In group ATRA+I/R+P,Nrf2/ARE signaling pathway blocker ARTA 6 mg/kg was intraperitoneally injected once a day for 3 consecutive days,and the model of lung I/R injury was established at 2 h after the last administration.In group I/R+P and group ARTA+I/R+P,while the model of lung I/R injury was established,propofol 30 mg · kg-1 · h-1 was infused via the caudal vein until 120 min of reperfusion.The rats were sacrificed at 120 min of reperfusion and then the lungs were removed for examination of the pathological changes which were scored and for measurement of wet/dry weight ratio (W/D ratio),superoxide dismutase (SOD) activity (by xanthine oxidase method),malondialdehyde (MDA) content (using thiobarbituric acid method) and expression of Nrf2 and heme oxygenase-1 (HO-1) protein (by Western blot).Results Compared with group S,the pathological scores,W/D ratio and MDA content were significantly increased,and the activity of SOD was decreased in I/R and ATRA+I/R+P groups,and the expression of Nrf-2 and HO-1 was significantly up-regulated in I/R,I/R+P and ATRA+I/R+P groups (P＜0.05).Compared with group I/R,the pathological scores,W/D ratio and MDA content were significantly decreased,the activity of SOD was increased,and the expression of Nrf-2 and HO-1 was up-regulated in group I/R+P (P＜0.05),and no significant change was found in the indexes mentioned above in group ARTA+I/R+P (P＞0.05).Compared with group I/R+P,the pathological scores,W/D ratio and MDA content were significantly increased,the activity of SOD was decreased,and the expression of Nrf-2 and HO-1 was down-regulated in group ARTA+ I/R+P (P＜0.05).Conclusion Nrf2/ARE signaling pathway activation is involved in propofol-induced reduction of lung I/R injury in aged rats.