Protective effects of histone deacetylase inhibitor on survival and permeability of pulmonary microvascular endothelium in 50% TBSA full-thickness burn in rat model
Abstract：Objective To test whether administration of HDACI (VPA and 2M2P), without fluid resuscitation, can improve permeability of microvascular endothelium and survival rate in shock rats with 50% TBSA full-thickness burn injury.Methods Rats were subjected to 50% TBSA full-thickness burn injury. The back, legs, abdominal and right cervical area of male Sprague-Dawley(SD) rats were shaved under anesthesia. After that, the rats were subjected to a 50%(50.4%±3.8%)total body surface area(TBSA)full-thickness flame injury under anesthesia. Seventy-eight male rats were randomized divided into:① no burn shock (sham) group, ② burn shock with no resuscitation (NR) group, ③ burn shock with valproic acid (VPA) group, and ④ burn shock with 2-methyl-2-pentenoic acid (2M2P) group. Both VPA and 2M2P groups were injected immediately after burn shock at 300 mg/kg separately. After that,both the average survival time and survival rates were recorded. In another group of 160 rats, survival rats at 6 hour were examined for vascular permeability of organs with Evans blue staining method. Tissues of heart, liver, kidneys and jejunum were harvested for determination of water contents by oven drying method. After this process, blood samples were taken from ventral aorta at baseline, for the measurement of levels of TNF-α and 2,3- DPG in plasma. Results VPA enhanced the duration of survival. After burn shock, 50%(VPA) pretreated rats were alive versus 0% in NR group at 12 hours. In both VPA and 2M2P groups, the survival of severely burn shock rats increased, the pro-survival effects of VPA administration were dramatic. The average survival time in VPA group was 13.56 h significantly longer than those in 2M2P group(8.51 h) and scalded group(6.21 h) (P<0.05).The water contents and organ vascular pearmeability in the three groups of rats were increased, lower in VPA group than in 2M2P group and NR group. The levels of TNF-α and 2,3-DPG in plasma of the rats were also determined. Conclusions The histone deacetylase inhibitor(VPA)offers considerable protection in severe burn shock and improves permeability of microvascular endothelium perfusion of crucial organs in 50% TBSA burn injury. The possible mechanisms of VPA is potentially relevant with decreasing the level of TNF-α and incrensing the level of 2,3-DPG.
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