Therapeutic and preventive effect of dexamethasone on endotoxin shock in rabbits and its relationship with TNF / 第三军医大学学报

ABSTRACT

Objective　To explore the effect of dexamethasone (Dex) given with the intention of prevention or treatment on endotoxin shock in rabbits and its relationship with tumor necrosis factor (TNF). Methods　Fifty-three health rabbits were divided into 4 groups, including normal control (n=13), endoxin shock group (n=16), preventive Dex group (n=12) and therapeutic Dex group (n=12). Except normal control was given with saline, the other 3 groups were administered with lipopolysaccharide (LPS) infusion, and the preventive Dex group was treated with Dex (5 mg/kg body weight) 30 min before LPS infusion and the therapeutic Dex group 20 min after LPS infusion. Mean arterial blood pressure (MABP), survival rate, TNF level in circulatory blood and other parameters were detected. Results　In preventive and therapeutic Dex groups, MABP was increased and survival rate was reduced compared with the animals from endoxin shock group (P<0.05, P<0.01), and TNF activity in the circulating blood was significantly suppressed (P<0.01). In addition, dexamethasone administration could alleviate the elevation of plasma glucagon, glucose, lactic acid, and β-glucironidase (P<0.05, P<0.01) in shocked animals. It was also found that administration of dexamethasone in vitro prevented the release of TNF by Kupffer cells. Conclusion　These results indicate that the preventive and therapeutic effect of dexamethasone on endotoxin shock, which may relate to its direct inhibition of the release of TNF induced by LPS.