The study of dose-effect relationship of valproic acid on protecting heart and brain in a rodent model of severe burn injury

Wang Xiaoqing; Luo Hongmin; Liu Guiyang; Ma Jianli; Jia Yanhua; Hu Sen

doi:10.3969/j.issn.1672-8521.2014.01.007

Abstract：Objective:To investigate the dose-effect relationship of valproic acid on protecting vital organs in rats with severe burn inj ury. Methods:Forty-eight Grade Ⅱ male SD rats were randomly divided into 4 groups:scald group and low,medium and high dose of VPA groups,with 1 2 rats in each group. The rats were exposed to 5 5%TBSA of full-thickness thermal injury by immersing the back,both hindlegs and the abdomen in 80 ℃ water for 1 5 ,1 5 and 8 seconds respectively,and the third degree scald inj ury was verified by pathological examination. After the injury,animals received subcutaneous injection of normal saline (0.2 ml)or VPA 100,200 and 300 mg/kg, respectively. The rats were sacrificed,the blood,brain and heart tissues were harvested for examination 2 hours post-inj ury. Plasma creatine kinase MB (CK-MB)and neuron-specific enolase (NSE)levels were assayed by auto-matic biochemical analyzer or ELISA respectively. Histone H3K9 acetylation (Ac-H3K9)level was assayed by Western blotting. Results:Low dose of VPA had no obvious effect on plasma CK-MB and NSE levels (P>0.05), but medium and high dose of VPA could decrease the two indicators significantly (P<0.05).The high dose of VPA increased plasma CK-MB levels more obviously compared to medium dose of VPA (P<0.05),but no statis-tical difference in plasma NSE level between high and medium dose of VPA groups (P>0.05).VPA also showed a dose-dependent increase in Ac-H3K9 level in the heart and brain tissues (P<0.05),but no significant difference was observed between the results of high and medium dose of VPA groups (P>0.05).Conclusions:The protec-tive effect of VPA on brain and heart in burn shock may depend on its dose. Subcutaneous injection of 200 mg/kg VPA to severely burned rats is effective in protecting their vital organs.