Effects of extracellular signal-regulated kinase inhibition by AG126 on tissue tumor necrosis factor-alpha expression and multiple organ dysfunction in rats with postburn Staphylococcus aureus sepsis / 中华外科杂志
Chinese Journal of Surgery
;
(12): 391-395, 2004.
Artículo
en Chino
| WPRIM
| ID: wpr-299938
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of extracellular signal-regulated kinase (ERKs) inhibition by AG126 on tissue tumor necrosis factor-alpha (TNF-alpha) expression and multiple organ dysfunction in rats with postburn Staphylococcus aureus sepsis and its potential signal regulating mechanism.</p><p><b>METHODS</b>To reproduce postburn sepsis model, male Wistar rats were inflicated with 20% total body surface area third-degree scald followed by Staphylococcus aureus challenge. 34 rats were randomly divided into four groups as follows normal control group (n = 6), scald control group (n = 6), postburn sepsis group (n = 12), and AG126 treatment group (n = 10). Tissue samples from the liver, kidneys and lungs were collected to determine phosphorylated ERKs by Western blot analysis, and TNF-alpha mRNA expression as well as its protein levels.</p><p><b>RESULTS</b>It was revealed that phosphorylated ERKs in the liver, lungs, and kidneys from postburn septic animals were up-regulated rapidly at 0.5 - 2.0 hours, being 1.94-fold (P < 0.05), 2.86-fold (P < 0.01), and 1.41-fold at 2.0 hours compared to normal controls, respectively. Treatment with AG126 could significantly reduce phosphorylated ERKs in lung tissue by 70.6% (P < 0.01) at 2.0 hours postburn sepsis, and almost completely inhibited ERKs activation in the liver and kidneys at various time points. Meanwhile, both TNF-alpha mRNA and protein expressions in the liver, lungs, and kidneys were significantly decreased in AG126-treated group following septic challenge (P < 0.05 or 0.01). In addition, 2.0 hours after Staphylococcus aureus infection, treatment with AG126 markedly improved hepatic and renal function parameters, including serum ALT, AST, Cr, as well as BUN levels (P < 0.05 or 0.01), together with significant decrease in pulmonary myeloperoxidase activity, compared to those without AG126 treatment.</p><p><b>CONCLUSION</b>These data suggested that ERKs signal transduction might be involved in the pathogenesis of systemic inflammatory response and multiple organ dysfunction in postburn gram-positive bacterial sepsis. Early treatment with AG126 could significantly down-regulate TNF-alpha mRNA expression as well as protein levels in vital organs and attenuate multiple organ dysfunction induced by scald injury combined with Staphylococcus aureus challenge.</p>
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Farmacología
/
Infecciones Estafilocócicas
/
Quemaduras
/
ARN Mensajero
/
Distribución Aleatoria
/
Expresión Génica
/
Western Blotting
/
Factor de Necrosis Tumoral alfa
/
Ratas Wistar
/
Tirfostinos
Tipo de estudio:
Estudio pronóstico
Límite:
Animales
Idioma:
Chino
Revista:
Chinese Journal of Surgery
Año:
2004
Tipo del documento:
Artículo
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