Valproic Acid Treatment Inhibits Vasopermeability and Improves Survival in Rats With Lethal Scald Injury
| Autor: | Yue-Long Dai, Fu-Bo Tang, Yanguang Li, Hong-Min Luo, Sen Hu, Wenhua Zhang, Hai-Bin Wang, Rui-Liu, Guo-Yong Zhou |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A medicine.drug_class Cell Culture Techniques Vascular permeability Pharmacology Proinflammatory cytokine Capillary Permeability Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Enzyme Inhibitors Histone Acetyltransferases Peroxidase Valproic Acid Lung biology business.industry Rehabilitation Histone deacetylase inhibitor Endothelial Cells 030208 emergency & critical care medicine Rats Vascular endothelial growth factor Disease Models Animal medicine.anatomical_structure chemistry Acetylation 030220 oncology & carcinogenesis Myeloperoxidase Immunology Emergency Medicine biology.protein Surgery business Burns medicine.drug |
| Zdroj: | Journal of burn careresearch : official publication of the American Burn Association. 39(2) |
| ISSN: | 1559-0488 |
| Popis: | The aim of this study was to examine whether administration of valproic acid (VPA), a histone deacetylase inhibitor, inhibits proinflammatory mediators and ameliorate visceral vasopermeability both in a rat model of major burn, and also in rat cultured endothelial cells stimulated with permeability evoking mediators. SD rats were subjected to a 50% TBSA full-thickness scald injury, and treated with either saline or VPA (300 mg/kg) intraperitoneally. Pulmonary vascular endothelial growth factor (VEGF), myeloperoxidase (MPO), pulmonary microvascular permeability, water content, and acetylation of histone H3K9 of lungs were evaluated. In addition, pulmonary microvascular endothelial cells (PMECs) from male SD rats were cultured. With then, MPO, VEGF, histone acetylation, and the permeability of PMECs were investigated. Lethal scald injury resulted in a significant increase in microvascular permeability and water content of lung, accompanied by a significant elevation of the content of VEGF and activity of MPO, and a decrease of histone acetylation. VPA treatment significantly alleviated the microvascular permeability and water content of lung, lowered the levels of VEGF and MPO, and promoted acetylation of histone H3K9 following scald injury. Moreover, VPA reduced permeability of monolayer PMECs subjected to scald serum challenge, reduced the level of MPO and VEGF in supernatants, and promoted acetylation of histone H3K9 in PMECs. These results indicated that VPA can protect pulmonary microvascular endothelial barrier, alleviate proinflammatory mediators-evoked vascular hyperpermeability and tissue edema and improve the survival rate of rats subjected to lethal scald injury. |
| Databáze: | OpenAIRE |
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