Abstract: Background Sodium valproic acid (VPA) has made great progress in the study of cardiac function protection in the early stage of severe scald injury. Hypoxia-inducible factor-1α (HIF-1α) is closely related to cardiomyocyte apoptosis, and the mechanism of the role of VPA and HIF-1α in the apoptosis of cardiomyocytes in severe scald injury remains to be explored.Objective To investigate whether VPA inhibits early cardiomyocyte apoptosis in lethally scalded rats by affecting HIF-1α. Methods 48 male SD rats were randomly divided into normal + 0.9% NaCl group (NN group), scald + 0.9% NaCl group (SN group), scald + VPA group (SV group), 16 rats in each group; the back of the rat was immersed in 100 ℃ boiling water for 15 s, and the abdomen for 8 s to cause a third-degree scald with a total body surface area of 50%, and the NN and SN group were intraperitoneally injected with 0.25 ml of NaCl, and the SV group was intraperitoneally given VPA treatment (300 mg/kg, dissolved in 0.25 ml of 0.9% NaCl) immediately after the injury. Immediately after injury, the NN and SN groups were injected intraperitoneally with 0.25 ml of NaCl, and the SV group was treated with VPA (300 mg/kg dissolved in 0.25 ml of 0.9% NaCl) intraperitoneally. The animals were executed at 3h and 6h after injury, respectively. Blood was taken from the abdominal aorta, and creatine kinase isoenzyme (CK-MB) levels were measured; myocardial tissue was taken, and pathological changes and cardiomyocyte apoptosis were observed, and nitric oxide (NO) content and cysteine proteinase-3 (caspase-3) activity were measured, as well as the levels of hypoxia-inducible factor-1α(HIF-1α), inducible nitric oxide synthase (iNOS), BCL2/adenovirus E1B interacting protein 3 (BNIP3), and caspase-3 protein expression levels in myocardial tissues. Results Compared with the NN group, plasma CK-MB level, cardiomyocyte apoptosis rate, caspase-3 activity, NO content, caspase-3, HIF-1α, iNOS, and BNIP3 protein expression levels were significantly increased in the SN group at 3h and 6h post-injury (P all <0.05); compared with the SN group, CK-MB level, cardiomyocyte apoptosis rate, caspase-3 activity, NO content were significantly decreased, and caspase-3, HIF-1α, iNOS, and BNIP3 protein expression levels were significantly reduced in the SV group (P all <0.05). Conclusions: VPA inhibits cardiomyocyte apoptosis and attenuates myocardial injury by down-regulating the expression of HIF-1α in myocardial tissues of lethally scalded rats.