The activation of α₂-adrenergic receptor in the spinal cord lowers sepsis-induced mortality
The Korean Journal of Physiology and Pharmacology
;
: 495-507, 2017.
Artículo
en Inglés
| WPRIM
| ID: wpr-728762
ABSTRACT
The effect of clonidine administered intrathecally (i.t.) on the mortality and the blood glucose level induced by sepsis was examined in mice. To produce sepsis, the mixture of D-galactosamine (GaLN; 0.6 g/10 ml)/lipopolysaccharide (LPS; 27 µg/27 µl) was treated intraperitoneally (i.p.). The i.t. pretreatment with clonidine (5 µg/5 µl) increased the blood glucose level and attenuated mortality induced by sepsis in a dose-dependent manner. The i.t. post-treatment with clonidine up to 3 h caused an elevation of the blood glucose level and protected sepsis-induced mortality, whereas clonidine post-treated at 6, 9, or 12 h did not affect. The pre-treatment with oral D-glucose for 30 min prior to i.t. post-treatment (6 h) with clonidine did not rescue sepsis-induced mortality. In addition, i.t. pretreatment with pertussis toxin (PTX) reduced clonidine-induced protection against mortality and clonidine-induced hyperglycemia, suggesting that protective effect against sepsis-induced mortality seems to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Moreover, pretreatment with clonidine attenuated the plasma tumor necrosis factor α (TNF-α) induced by sepsis. Clonidine administered i.t. or i.p. increased p-AMPKα1 and p-AMPKα2, but decreased p-Tyk2 and p-mTOR levels in both control and sepsis groups, suggesting that the up-regulations of p-AMPKα1 and p-AMPKα2, or down-regulations of p-mTOR and p-Tyk2 may play critical roles for the protective effect of clonidine against sepsis-induced mortality.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Plasma
/
Médula Espinal
/
Glucemia
/
Mortalidad
/
Factor de Necrosis Tumoral alfa
/
Clonidina
/
Sepsis
/
Proteínas de Unión al GTP
/
Toxina del Pertussis
/
Glucosa
Tipo de estudio:
Estudio pronóstico
Límite:
Animales
Idioma:
Inglés
Revista:
The Korean Journal of Physiology and Pharmacology
Año:
2017
Tipo del documento:
Artículo
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