Background Patients are prone to have a systemic inflammatory response syndrome (SIRS) after severe burns. SIRS can cause capillary leakage, and lead to multiple organ dysfunction, which seriously affects the prognosis. Histone acetylation plays an important role in the progression of capillary leakage. As an inhibitor of deacetylation, sodium valproate may protect the organ in burnt patients.
Objective To investigate the protective effect and mechanism of histone deacetylase inhibitors called VPA on microvascular endothelial barrier in rats after severe burn injury.
Methods Rats were randomly divided into four groups: normal+0.9% NaCl normal saline (NN group), normal+VPA (NV group), scald+0.9% NaCl normal saline (SN group), scald+VPA (SV group) with 16 rats in each group. Rats were sacrificed at 2 h and 6 h after injury. Pulmonary microvascular permeability, tissue water content, vascular endothelial growth factor (VEGF), myeloperoxidase (MPO) activity and acetylation of histone H3K9 lysine (Ac-H3K9) were detected in lung tissues.
Results Compared with the NN group, lung microvascular permeability and lung tissue moisture content increased significantly in the SN group at 2 h and 6 h (all P < 0.05) ; At the same time, the level of VEGF, the activity of MPO, and the expression of Ac-H3K9 also significantly increased (all P < 0.05). However, compared with SN group, they all decreased in the SV group at 6 h after injury (all P < 0.05).
Conclusion VPA can reduce the damage of pulmonary micro-vascular endothelial barrier caused by severe scald, and its mechanism may be related to the inhibitory effect on VEGF and MPO.
DownLoad: