[Protective effects of valproic acid on gut barrier function after major burn injury and its mechanism].
摘要
OBJECTIVE: To investigate the potential protective effects of valproic acid (VPA) on gut barrier function after major burn injury in rats and its mechanism. METHODS: Forty male Sprague-Dawley (SD) rats were divided into sham + normal saline (NS), sham + VPA, scald + NS, and scald + VPA groups, with 10 rats in each group. Rat with 55% total body surface area (TBSA) third-degree severe-burns model was reproduced by immersing into 80 °C water, and the rats in sham groups were given sham-burns by immersing into 37 °C water. The rats after severe-burns were immediately treated with 0.25 mL of 300 mg/kg VPA or NS by subcutaneous injection. Rats were sacrificed at 2 hours and 6 hours after injury, and abdominal aortic blood and ileal tissue were harvested. The levels of vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA). The intestinal permeability was evaluated by fluorescein isothiocyanate-dextran (FITC-dextran) determination. The histomorphological changes in gut barrier were evaluated by Chiu grading system. Levels of acetylated lysine at the ninth position of histone 3 protein (Ac-H3K9), hypoxia-inducible factor 1α (HIF-1α), zona occludens 1 (ZO-1) and myosin light chain kinase (MLCK) were determined by immunofluorescence staining and Western Blot. RESULTS: Compared with sham + NS group, rats in scald + NS group showed intestinal mucosal damage 2 hours after burn injury, as well as increased mucosal permeability, protein expression levels of HIF-1α, VEGF, MLCK, and lowered levels of AC-H3K9 and ZO-1. These changes were much more prominent at 6 hours after injury. VPA treatment significantly attenuated the burn-induced intestinal damage. Compared with scald + NS group, the protective effects in scald + VPA group was not evident at 2 hours after injury; however, intestinal damage was much less severe at 6 hours after injury (Chiu score: 2.03±0.27 vs. 3.12±0.15), intestinal permeability was significantly decreased [FITC