To study the effect of histone deacetylase inhibitor valproate on cerebral injury of the rats with 50% total body surface area (TBSA) full thickness burn.

Eighty male clean-grade SD rats were divided into four groups according to the random number table method: sham injury control group, simple scald group, 2-methyl-2-pentenoic acid (2M2P) group and sodium valproate (VPA) group, with 20 rats in each group. Rats in the sham injury group were immersed in a 37 ℃ water bath to prepare a sham injury model. In the simple scald group, 2M2P group and VPA group, the rats were immersed in a 96 ℃ water bath for 15 s on the back, 15 s on both lower limbs, and 8 s on the abdomen to create 50% TBSA full thickness burn rats models. Immediately after scalding, the 2M2P group and the VPA group were intraperitoneally injected with 300 mg/kg 2M2P and VPA, respectively, and the sham injury control group and the simple scald group were intraperitoneally injected with 3 mL/kg 0.9% sodium chloride solution, respectively. Rats in each group were sacrificed by abdominal aorta blood sampling at 4 and 8 h after scalding, respectively. The expression level of S-100β protein in brain tissue was detected by enzyme-linked immunosorbent assay (ELISA), the water content of rat brain tissue was determined by dry/wet weight method, and the protein expression levels of heat shock protein (HSP) 70, histone H3 lysine 9 acetylation (H3K9ac) and hypoxia-inducible factor-1α (HIF-1α) in brain tissue were detected by Western blotting. Another 80 rats were used to observe the survival rate of 4 and 24 h after scald in each group (rat grouping, scald model prepare and treatment plan were the same as above). Data were compared with one-way ANOVA, t test and chi-square test.

At 4 and 8 h after scalding, there were statistically significant differences in the levels of S-100β protein and water content in the brain tissue of the four groups (P< 0.05). At 4 and 8 h after scalding, the expression levels of S-100β protein and water content in the brain tissue of the rats in the simple scald group, 2M2P group and VPA group were statistically significantly different from those in the sham-injured control group(P<0.05). At 4 and 8 h after scalding, the expression levels of S-100β protein and water content in the 2M2P group and the VPA group were statistically significantly different from those in the simple scalding group (P<0.05). At 4 and 8 h after scalding, the expression levels of S-100β protein in the brain tissue of the VPA group were (0.54±0.05), (0.79±0.05) μg/L, respectively, compared with [(1.02±0.07), (1.41±0.08) μg/L] in the 2M2P group were significantly decreased, and the differences were statistically significant (t=2.369, 2.251; P<0.05). At 4 and 8 h after scalding, the water content of brain tissue in the VPA group were (78.62±0.58)% and (81.25±0.57)%, respectively, which were significantly lower than those in the 2M2P group [(80.15±0.64)% and (83.15±0.61)%], the differences were statistically significant (t=2.054, 2.191; P<0.05). At 4 and 8 h after scalding, the protein expression levels of HSP70, H3K9ac and HIF-1α in the brain tissue of the four groups of rats were compared, and the differences were statistically significant (P<0.05). At 4 and 8 h after scalding, the protein expression levels of HSP70, H3K9ac and HIF-1α in the brain tissue of the rats in the simple scald group, the 2M2P group and the VPA group were statistically significantly different from those in the sham-injured control group (P<0.05). At 4 and 8 h after scalding, the protein levels of HSP70, H3K9ac and HIF-1α in the brain tissue of the 2M2P group and VPA group were statistically significantly different from those in the simple scalding group (P<0.05). At 4 and 8 h after scalding, the levels of HSP70 protein in the brain tissue of the VPA group were 0.63±0.05, 0.81±0.04, respectively, compared with the 2M2P group (0.41±0.03, 0.59±0.04), the level of HSP70 protein in the brain tissue of the rats in the VPA group increased significantly, and the differences were statistically significant (t=2.413, 2.152; P<0.05). At 4 and 8 h after scalding, the levels of H3K9ac protein in the brain tissue of the VPA group were 1.26±0.09, 1.58±0.07, which were higher than those in the 2M2P group (1.06±0.06, 1.24±0.07), the differences were statistically significant (t=2.031, 2.167; P<0.05); the expression levels of HIF-1α protein in the VPA group were 2.23±0.21 and 1.86±0.23, respectively, which were significantly lower than those in the 2M2P group (3.01±0.24, 2.74±0.21), the differences were statistically significant (t=2.157, 2.425; P<0.05). At 4 and 24 h after scalding, the survival rates of the rats in the simple scald group were 80.0% (16/20) and 0 (0/20); those in the 2M2P group were 90% (18/20) and 20% (4/20); the VPA group was 100% (20/20) and 40% (8/20). At 4 and 24 h after scalding, the survival rates of the rats in the VPA group and 2M2P group were significantly higher than those in the simple scald group, and the differences were statistically significant (χ²=11.31, 11.96; P<0.05). At 4 and 24 h after scalding, the survival rates of rats in the VPA group were higher than those in the 2M2P group, and the differences were statistically significant (χ²=11.32, 12.05; P<0.05).

VPA can reduce the brain injury of 50% TBSA full thickness burn rats and improve the survival rate. The mechanism may be related to VPA reduces the protein expression level of S-100β and the water content of brain tissue, promots the expression of HSP70 and H3K9ac proteins in brain tissue and inhibits the activity of HIF-1α.