| Objective: To replicate a rat model of burn shock with 50% TBSA full-thickness scald injury and to investigate whether Sodium valproate administration can improve the visceral microvascular vascular permeability and functional parameters in rats with a 50% TBSA full-thickness burn.Methods: Male Sprague-Dawley rats 240~270g, were subjected to a (50.4±3.8)% TBSA full-thickness flame injury, and then randomly divided into four groups:①sham group (water bath in 37℃).②scald group (water bath in 80℃on rat back and both lower extremities 15s and abdomen 8s).③VPA group (valproic aicd ) and④2M2P group(2-methyl-2-pentenoic acid, was structural VPA analog with limited HDAC inhibiting activity. Both VPA and 2M2P were dissolved in normal saline, prepared daily and subcutaneously injected 300mg/kg immediately after scald. A small incision was made on the right cervical area of rats. The carotid artery were isolated, and cannulated using polyethylene tubing.The catheter was attached to a pressure transducer which allowed instantaneous measurement of the mean arterial pressure (MAP). The blood samples were taken before scald and 2,4,6 and 12 hour after scald for the measurement of the plasma levels of creatinine (Cr), alanine aminotransferase (ALT) and isoenzyme of creatine kinase(CK-MB), as well as the TNF-α. Visceral microvascular permeability was examined with evans blue staining method. The tissues water contents of heart, liver and kidney were determined by the method of dry/wet.Results: A rat model of burn shock with 50% TBSA full-thickness scald injury was replicated in the present study. MAP was drastically decreased to 50mmHg lever in 2 hours in NR group after 50% TBSA full-thickness scald injury. Both VPA and 2M2P increased the survival of severely burn shock rats, the pro-survival effects of VPA administration were more dramatic. The average survival time of VPA group was 13.56 h significantly longer than those of 2M2P group (8.51h) and scald group(6.21 h),(P<0.05). Survival rates for 12 h after scald were in following order: VPA group (50%)>2M2P (16.7%)>scald group(0%). The levels of ALT,Cr and CK-MB in all groups increased significantly after scald. The levels of ALT and Cr of VPA group were obviously lower than those of scald group and 2M2P group at 2h,6h,12h after scald(P<0.05). The level of CK-MB of VPA group was lower than those of scald group and 2M2P group at 2h,4h,6h after scald(P<0.05). The tissue concentration of Evans blue in heart, liver and kidney of three groups were apparently increased after scald, but which of VPA group were much lower than those of the 2M2P group and scald group. The water contents of heart, kidney in VPA group were significantly lower than those of scald group and 2M2P group, but still higher than those of sham group. The levels of TNF-αand 2,3- DPG level in plasma were also determined.Conclusion: The results indicated that VPA offer potential value in treatment of burn shock by inhibition of TNF-αlevels and visceral microvascular permeability, alleviation of the visceral edema and organ dysfunction, promotion of survival rate for 12h after scald in rats subjected to 50% TBSA full-thickness scald.
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