Role of ROS in emulsified isoflurane postconditioning-induced promotion of Nrf2∕ARE signaling pathway activation in rats with myocardial injury
10.3760∕cma.j.issn.0254-1416.2016.09.005
- VernacularTitle:ROS在乳化异氟醚后处理促进心肌损伤大鼠Nrf2∕ARE信号通路激活中的作用
- Author:
Liping HUANG
;
Wei CHEN
;
Haiying WANG
;
Peng XU
;
Xingkui LIU
;
Tian YU
- Keywords:
Reactive oxygen species;
Isoflurane;
Fat emulsions,intravenous;
Myocardial reperfusion injury;
NF-E2 related factor-2;
Response element
- From:
Chinese Journal of Anesthesiology
2016;36(9):1052-1057
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of reactive oxygen species ( ROS ) in emulsified isoflurane postconditioning?induced promotion of nuclear factor?E2 related factor 2 ( Nrf2 )∕antioxidant re?sponse element ( ARE) signaling pathway activation in rats with myocardial injury. Methods Healthy male Sprague?Dawley rats, aged 16-20 weeks, weighing 250-300 g, were heparinized and anesthetized. Their hearts were excised and perfused in a Langendorff apparatus with K?H solution. Eighty isolated rat hearts were divided into 5 groups ( n=16 each) using a random number table: control group ( group C);ischemia?reperfusion (I∕R) group; emulsified isoflurane postconditioning group (group EIP); fat emulsion postconditioning group (group FEP); N?(2?mercaptopropionyl)?glycine (a ROS scavenger) plus emulsi?fied isoflurane postconditioning group ( group N+EIP ) . Group C was perfused with K?H solution for 100 min, and the other 4 groups were subjected to 40 min of ischemia followed by 60 min of reperfusion. EIP and FEP groups were perfused for 2 min with K?H solution containing 1?68 mmol∕L emulsified isoflurane and 712 mg∕L intralipid, respectively, starting from the onset of reperfusion, and then continuously per?fused with K?H solution for 58 min. Group N+EIP was perfused for 3 min with K?H solution containing N?(2?mercaptopropionyl)?glycine 2 mmol∕L, and then emulsified isoflurane postconditioning was performed. Heart rate ( HR ) , left ventricular developed pressure ( LVDP ) , left ventricular end?diastolic pressure (LVEDP) and the maximum rate of increase of left ventricular pressure (+dp∕dtmax) were recorded at the end of equilibration and of reperfusion. At 5 min of reperfusion and the end of reperfusion, myocardial specimens were obtained for determination of ROS content. At the end of reperfusion, myocardial specimens were obtained for examination of the ultrastructure of myocardial cells and for determination of the expression of Nrf2, heme oxygenase?1 ( HO?1 ) , quinone oxidoreductase 1 ( NQO1 ) and superoxide dismutase?1 ( SOD?1) protein and mRNA in myocardial tissues. Mitochondrial injury scores ( Flameng scores) were e?valuated. Results Compared with group C, HR, +dp∕dtmax and LVDP were significantly decreased, LV?EDP , mitochondrial Flameng scores and ROS contents were increased, and the expression of Nrf2, HO?1, NQO1 and SOD?1 protein and mRNA was down?regulated at the end of reperfusion in I∕R group ( P<0?05) . Compared with group I∕R, HR, +dp∕dtmax and LVDP were significantly increased, LVEDP, mitochondrial Flameng scores and ROS contents were decreased, and the expression of Nrf2, HO?1, NQO1 and SOD?1 protein and mRNA was up?regulated at the end of reperfusion in group EIP ( P<0?05) , and no significant changes in the parameters mentioned above were found in group N+EIP ( P>0?05) . Compared with group EIP, HR, +dp∕dtmax and LVDP were significantly decreased, LVEDP and mitochondrial Flameng scores were increased, ROS contents at 5 min of reperfusion were decreased, ROS contents at the end of reperfu?sion were increased, and the expression of Nrf2, HO?1, NQO1 and SOD?1 protein and mRNA was down?regulated in group N+EIP ( P<0?05) . The degree of myocardial injury was reduced in group EIP as com?pared with group I∕R. There was no significant difference in the degree of myocardial injury between group N+EIP and group I∕R. Conclusion The mechanism by which emulsified isoflurane postconditioning pro?motes Nrf2?ARE signaling pathway activation is totally related to ROS in rats with myocardial injury.
