Simvastatin reduces burn injury-induced splenic apoptosis via downregulation of the TNF-α/NF-κB pathway.
Ann Surg
; 261(5): 1006-12, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-24950285
ABSTRACT
OBJECTIVE:
Recent studies have suggested that epidermal burn injuries are associated with inflammation and immune dysfunction. Simvastatin has been shown to possess potent anti-inflammatory properties. Thus, we hypothesized that simvastatin protects against burn-induced apoptosis in the spleen via its anti-inflammatory activity.METHODS:
Wild-type, tumor necrosis factor alpha knockout (TNF-α KO) and NF-κB KO mice were subjected to full-thickness burn injury or sham treatment. The mice then were treated with or without simvastatin, and the spleen was harvested to measure the extent of apoptosis. Expression levels of TNF-α and NF-κB were also determined in spleen tissue and serum.RESULTS:
Burn injury induced significant splenic apoptosis and systemic cytokine production. Simvastatin protected the spleen from apoptosis, reduced cytokine production in the serum, and increased the survival rate. Simvastatin decreased burn-induced TNF-α and NF-κB expression in the spleen and serum. TNF-α and NF-κB KO mice demonstrated lower levels of apoptosis in spleen in response to burn injury. Simvastatin did not further decrease burn-caused apoptosis and mortality in either strain of KO mice.CONCLUSIONS:
Simvastatin reduces burn-induced splenic apoptosis via downregulation of the TNF-α/NF-κB pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Baço
/
Queimaduras
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NF-kappa B
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Fator de Necrose Tumoral alfa
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Apoptose
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Sinvastatina
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Anti-Inflamatórios
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article