Role of peroxisome proliferator-activated receptor-γ in sevoflurane postconditioning reduce myocardial ischemia-reperfusion injury in mice

Abstract

Objective To observe the effect of sevoflurane on peroxisome proliferator-activated receptor-γ (PPAR-γ) in reperfusion myocardium and study the role of PPAR-γ in sevoflurane postconditioning against myocardial ischemia-reperfusion injury. Methods Male C57BL/6 mice were randomly allocated into four groups (n=5 each): Control group, Sevoflurane postconditioning (SPostC) group, Sevoflurane postconditioning+ PPAR-γ inhibitor (SPostC+ GW9662) group, PPAR-γ inhibitor (GW9662) group. All the groups establish the model of mice myocardial ischemia-reperfusion injury (30 min of ischemia and 120 min of reperfusion) in vivo, mice with myocardial ischemia received 3.4% sevoflurane for 15 min at the onset of reperfusion as the sevoflurane postconditioning, and all the groups inject inhibitor or placebo intraperitoneally at 30 min before ischemia. The heart rate (HR) and mean arterial pressure (MAP) of mice were measured before ischmia and after reperfusion. After experimental time out, heart of mice was excised, myocardial infarct size and PPAR-γ transcriptional activity were tested. Results Compared with Control group [(24.68±1.03)%; 0.081 8±0.006 0], myocardial infarct size [(18.70±2.58)%] reduced (P=0.000) significantly and PPAR-γ transcriptional activity (0.091 8±0.006 8) increased (P=0.026) in SPostC group, myocardial infarct size [(23.55±1.60)%; (23.14±1.46)%] and PPAR-γ transcriptional activity (0.082 4±0.005 7; 0.080 2±0.007 2) had a little change in SPostC+ GW9662 group (P=0.324, P=0.887) and GW9662 group (P=0.185, P=0.690) compared to Control group. HR and MAP before ischemiahave no difference between the groups (P=0.763, P=0.455), after reperfusion, the HR and MAP also have no difference between each groups (P=0.801, P=0.341). Conclusion Sevoflurane postconditioning can reduce myocardial infarct size via activating PPAR-γ and improving its transcriptional activity during myocardial ischemia-reperfusion injury. Key words: Peroxisome proliferator-activated receptor-γ; Sevoflurane postconditioning; Ischemia-reperfusion injury; Myocardial protection