Effect of ischemic preconditioning on HIF-1α and HO-1 in myocardium after myocardial ischemia-reperfusion injury in rats

Objective To investigate the effect of ischemic preconditioning(IP)on hypoxia inducible factor-1α(HIF-1α)and heme oxygenase-1(HO-1)in myocardium after myocardial ischemia-reperfusian(I/R)injury in rata and the mechanism.Methods Forty-eight male SD rata weighing 220-280 g were randomly divided into 4 groups(n= 12 each): group A sham operation;group B I/R;group C IP+I/R and group DIP+IR+HO-1 inhibitor.The animals were anesthetized with intraperitoneal 20% urethane 1 g/kg,tracheoatomized and mechanically ventilated.Myocardial ischemia was induced by 30 min occlusion of left anterior descending branch(LAD)of coronary artery followed by 120 min reperfusion,Ischemic preconditioning was induced by 3 episodes of5 min occlusion of LAD at 5 min intervals before myocardial ischemia.Group D received HO-1 inhibitor ZnPP Ⅸ10 mg/kg one day before IP.At the end of 120 min reperfusion the infarct size was measured,the expression of HIF-1α and HO-1 mRNA and protein,SOD and HO-1 activities and MDA content in myocardium and serum TNF-αand IL-6 concentrations were determined.Results Compared with sham operation group,I/R significantly increased MDA content in myocardium and serum TNF-α and IL-6 concentrations and decreased SOD activity in myocardium.Compared with I/R group,IP significantly decreased infarct size,increased HIF-1α and HO-1 mRNA and protein expression and HO-1 activity further and decreased serum TNF-α and IL-6 concentrations and myocardial MDA content in group C.In group D ZnPP Ⅸ pretreatment greatly increased infarct size which was significantly larger than that in group I/R and group IP+I/R.Conclusion IP can protect against myocardial I/R injury.Increase in HO-1 activity induced by HIP-1α may be involved in the underlying mechanism. Key words: Ischemic preconditioning; Myocardial reperfusion injury; Hypoxia-inducible factor 1; Heme oxygenase(decyclizing)