Role of Nrf2/ARE singling pathway in reduction of myocardial ischemia-reperfusion injury by zinc sulfate preconditioning in 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) singling pathway in reduction of myocardial ischemia-reperfusion (I/R) injury by zinc sulfate preconditioning in rats.Methods SPF healthy male Sprague-Dawley rats,weighing 250-280 g,aged 16-20 weeks,were used in this study.After the animals were anesthetized,their hearts were immediately removed and retrogradely perfused with an oxygenated K-H solution at 37 ℃ in a Langendorff apparatus.Forty isolated rat hearts were randomly divided into 4 groups (n=10 each)control group (group C),I/R group,zinc sulfate preconditioning group (group Zn) and zinc sulfate preconditioning plus Nrf2/ARE singling pathway blocker luteolin group (group Zn+Lut).After 20 min of equilibration,the hearts were continuously perfused for 100 min in group C,the hearts were perfused with 4 ℃ St.Thomas′ cardioplegic solution before ischemia and then subjected to 40 min global ischemia followed by 60 min reperfusion to establish the model of I/R in group I/R,200 μmol/L zinc sulfate 1.5 ml/kg was injected intraperitoneally,and 24 h later the model of I/R was established in group Zn,and in group Zn+Lut,the hearts were perfused for 3 min with K-H solution containing luteolin 50 μmol/L starting from the time point immediately before ischemia,and the other treatments were similar to those previously described in group Zn.Heart rate (HR),left ventricular end diabetic pressure (LVEDP),left ventricular developed pressure (LVDP) and the maximum rate of increase of left ventricular pressure (+dp/dtmax) were recorded at the end of equilibration and reperfusion.Coronary effluent was collected at the end of reperfusion to measure the levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA).The expression of heme oxygenase-1 (HO-1),quinone oxidoreductase (NQO1),superoxide dismutase 1 (SOD1) and Nrf2 in myocardial tissues was detected by Western blot.Results Compared with group C,HR,+dp/dtmax and LVDP were significantly decreased,LVEDP was increased,and the levels of LDH and MDA in coronary effluent were increased at the end of reperfusion in I/R and Zn+Lut groups,and the expression of NQO1,HO-1,Nrf2 and SOD1 was up-regulated in I/R,Zn and Zn+Lut groups (P0.05).Conclusion The mechanism by which zinc sulfate preconditioning reduces myocardial I/R injury is related to activation of Nrf2/ARE singling pathway in rats.