Effect of sevoflurane postconditioning on microRNA-133a expression during myocardial ischemia-reperfusion in mice

Objective To evaluate the effect of sevoflurane postconditioning on microRNA-133a(miR-133a)expression during myocardial ischemia-reperfusion(I/R)in mice. Methods Thirty adult male C57 mice, weighing 20-30 g, were randomized to 3 groups(n=10 each)using a random number table: control group(group C), I/R group, and sevoflurane postconditioning group(group SP). In I/R and SP groups, hearts from adult male C57 mice were exposed and subjected to 30 min of ischemia and 180 min of reperfusion in anesthetized mice according to the method described by Das et al.In group C, only thoracotomy was performed without ligation of the coronary artery.In group SP, 2.4% sevoflurane was inhaled for 5 min starting from the onset of reperfusion to perform sevoflurane postconditioning.At 180 min of reperfusion, blood samples from the femoral vein were collected for determination of serum lactic dehydrogenase(LDH)and creatine kinase(CK)activities using the colorimetric method.The mice were then sacrificed, and myocardial specimens were obtained for determination of myocardial infarct size, miR-133a and caspase-9 mRNA expression(by real-time reverse transcriptase polymerase chain reaction), and caspase-9 expression(by Western blot). Results Compared with group C, the serum LDH and CK activities and myocardial infarct size were significantly increased in I/R and SP groups, the expression of miR-133a was significantly down-regulated, and the expression of caspase-9 protein and mRNA was significantly up-regulated in group I/R, and the expression of miR-133a and caspase-9 protein and mRNA was significantly up-regulated in group SP(P<0.05). Compared with group I/R, the serum LDH and CK activities and myocardial infarct size were significantly decreased, the expression of miR-133a was significantly up-regulated, and the expression of caspase-9 protein and mRNA was significantly down-regulated in group SP(P<0.05). Conclusion The mechanism by which sevoflurane postconditioning inhibits cell apoptosis during myocardial I/R is related to up-regulation of miR-133a expression in mice. Key words: Anesthetics, inhalation; Ischemic postconditioning; Myocardial reperfusion injury; MicroRNAs