Role of heme oxygenase-1 in process of sevoflurane preconditioning attenuating hypoxla-reoxygenation iniury in cultured neonatal rat cardiomyocytes

Objective To investigate the role of heme oxygenase-1 (HO-1 ) in process of sevoflurane preconditioning attenuating hypoxia-reoxygenation (H/R) injury in cultured neonatal rat cardiomyocytes.Methods Primary cultured neonatal rat cardiomyocytes were randomly divided into four groups ( n ＝ 25 each):control group (group C),group H/R,sevoflurane preconditioning group(group S + H/R),and HO-1 inhibitor zinc protoporphyria (ZnPP) and sevoflurane preconditioning group(group ZnPP + S + H/R).In group H/R,the cardiomyocytes were exposed to 2 hours of hypoxia,followed by 1 hour of reoxygenation.Group S+ H/R received 2.5％ sevoflurane preconditioning for 20 minutes followed by 10 minutes of wash-out before H/R.ZnPP was added to the culture medium with final concentrations of 3 μMol/L 1 hour before sevoflurane preconditioning and H/R in group ZnPP +S + H/R.HO- 1 expression,apoptosis rate,concentration of free calcium ( [ Ca2 + ] i),mitochondrial membrane permeability transition pore (PTP),cytoohrome C ( Cyto C) expression and activities of lactate dehydrogenase (LDH) and creatine kinase (CK) in culture supernatant were detected after reoxygenation.Results Compared with group C,the expression of HO-1 and cytoplasmic Cyto C of cardiomyocytes were up-regulated,mitochondrial Cyto C was down-regulated,while the [Ca2+ ]i,opening degree of PIP,apoptosis rate and activities of LDH and CK in culture supernatant were increased in group H/R.Compared with group H/R,the expression of HO-1 and mitochondrial Cyto C of cardiomyocytes were up-regulated,cytoplasmic Cyto C was down-regulated,while the [Ca2+ ] i,opening degree of PTP,apoptosis rate and activities of LDH and CK in culture supernatant were decreased in group S + H/R.Compared with group S + H/R,the expression of HO-1 and mitochondrial Cyto C of cardiomyocytes were down-regulated,cytoplasmic Cyto C was up-regulated,while the [Ca2+ ]i,opening degree of PTP,apoptosis rate and activities of LDH and CK in culture supematant were increased in group ZnPP + S + H/R.Conclusion The up-regulation of HO-1 is involved in the process of sevoflurane preconditioning attenuating hypoxia-reoxygenation injury in cultured neonatal rat cardiomyocytes. Key words: Hene oxygenase-1 ; Cell hypoxia; Oxygen; Myocytes,cardiac; Sevoflurane