title: [The protective effect of valproic acid on myocardium in rats with lethal scald injury and its mechanism].
abstract: OBJECTIVE
  To investigate the protective effects of valproic acid (VPA) on myocardium in rats following lethal burn injury and its mechanism.
  
  
  METHODS
  Seventy-eight Sprague-Dawley (SD) rats were randomly assigned to four groups: sham-scald group (n=10), sham-scald + VPA group (n=10), scald group (n=29), and scald + VPA group (n=29). Rats in the latter two groups were subjected to 55% total body surface area (TBSA) third-degree burns by immersing the back of the trunk for 15 seconds, both lower extremities for 15 seconds, and the abdomen for 8 seconds in 80 centigrade water. Sham-scald rats were immersed in 37 centigrade water instead. Rats were then subcutaneously injected with VPA (300 mg/kg) or normal saline as control. Blood of 5 rats in each group was with drawn from the abdominal aorta at 6 hours after injury for measurement of plasma creatine kinase-MB (CK-MB) activities; then the rats were sacrificed and heart tissues were harvested for the measurement of acetylated histone H3 and activated caspase-3 by Western Blot. The remaining rats were used for 12-hour survival analysis.
  
  
  RESULTS
  Compared with sham-scald group, there was a significant increase in plasma CK-MB activities (5 438.0 ± 413.6 U/L vs. 2 881.0 ± 324.8 U/L, P<0.05) and activated caspase-3 protein levels in heart tissue (gray value: 1.75 ± 0.25 vs. 1.00 ± 0.18, P<0.05) and an significant decline in the acetylation levels of histone H3 (gray value: 0.55 ± 0.18 vs. 1.00 ± 0.20, P<0.05) after major burn injury. VPA treatment significantly reduced the plasma CK-MB activities [(4 018.0 ± 388.3) U/L], activated caspase-3 protein levels in heart tissue (gray value: 1.33 ± 0.20), and raised the acetylation levels of histone H3 (gray value: 2.20 ± 0.23, all P<0.05). Survival analysis by Kaplan-Meier curves showed that the survival was improved after VPA treatment, and the survival rate was increased from 0 to 50% at 12 hours (P<0.05).
  
  
  CONCLUSIONS
  VPA can attenuate cardiac injury and improve survival in a rodent model of lethal burn injury. These protective effects may be due to its inhibitory effects on histone deacetylase and caspase-3 activation.
authors.affiliation: Laboratory of Shock and Organ Dysfunction, Burn Institute, First Hospital Affiliated to the PLA General Hospital, Beijing 100048, China, Corresponding author: Hu Sen, Email: bs0425@163.com.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Luo
authors.forename: Sen
authors.initials: S
authors.lastname: Hu
authors.forename: Huiying
authors.initials: H
authors.lastname: Bai
authors.forename: Haibin
authors.initials: H
authors.lastname: Wang
authors.forename: Minghua
authors.initials: M
authors.lastname: Du
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Lin
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Lyu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Sheng
mesh_terms: D000107:Acetylation; D000818:Animals; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D052279:Creatine Kinase, MB Form / Q000097:blood; D004195:Disease Models, Animal; D006657:Histones / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D006657:Histones; D014635:Valproic Acid; D052279:Creatine Kinase, MB Form; C505410:Casp3 protein, rat; D053148:Caspase 3