Effects and mechanisms of sodium valproate on early survival and myocardial injury in rats with severe scald injury

Background Sodium valproate (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 myocardial injury, and the mechanism of action of VPA and HIF-1α in myocardial injury in severe scald injury remains to be explored.

Objective To investigate whether VPA attenuates early myocardial injury in severely scalded rats by affecting HIF-1α expression.

Methods Eighty-eight male SD rats were randomly divided into normal + 0.9% NaCl group (NN group, n=24), scald + 0.9% NaCl group (SN group, n=32), and scald + VPA group (SV group, n=32); Ⅲ ° scald with 50% of total surface area were caused by boiling water method, and NN and SN group were intraperitoneally injected with 0.25 mL of NaCl, and the SV group was intraperitoneally given VPA (300 mg/kg, dissolved in 0.25 mL of 0.9% NaCl) immediately after the injury. Eight rats in each group were executed at 3h and 6h after injury, and creatine kinase isoenzyme (CK-MB) levels were measured by taking blood from the abdominal aorta; myocardial tissues were taken for observation of myocardial tissue pathology and apoptotic cardiomyocytes, the levels of tumor necrosis factor-alpha (TNF-α), the expression levels of HIF-1α, BCL2/adenovirus E1B interacting protein 3 (BNIP3), and cleaved caspase-3; the 12-hour survival rate was observed in the remaining rats in each group.

Results Survival analysis showed that at 12 h after injury, SV group had a mean survival time of (550.00±17.32) min and a survival rate of 50%, which were superior to that of SN group (mean survival time of 400.00±29.76 min and a survival rate of 0%, P < 0.05). Compared with NN group, CK-MB, cardiomyocyte apoptosis rate, TNF-α, cleaved caspase-3, HIF-1α, and BNIP3 protein expression levels increased in SN group at 3h and 6h post-injury (all P < 0.05); compared with SN group, CK-MB, cardiomyocyte apoptosis rate, TNF-α were decreased, and cleaved caspase-3, HIF-1α, and BNIP3 protein expression levels were decreased in SV group (all P < 0.05); pathologic injuries were improved in SV group compared to SN group.

Conclusion VPA improves early post-injury survival and attenuates myocardial injury in severely scalded rats, which may be related to the down-regulation of HIF-1α expression in rat myocardial tissue.