地塞米松对家兔内毒素休克的防治作用及其与TNF的关系

Therapeutic and preventive effect of dexamethasone on endotoxin shock in rabbits and its relationship with TNF

目的 探讨预防性或治疗性给予地塞米松对家兔内毒素休克的防治作用及其与肿瘤坏死因子 (TNF)的关系。方法 5 3只健康家兔分为对照组 (n =13 ) ,内毒素休克组 (n =16) ,地塞米松预防组 (n =12 )及治疗组 (n =12 )。地塞米松预防组和治疗组动物于脂多糖 (LPS)输注前 3 0min或输注后 2 0min给予地塞米松 5mg/kg体重 ,观察MABP、动物死亡率、循环血中TNF水平及其它指标的变化。结果 与内毒素休克组相比 ,地塞米松预防和治疗组动物平均动脉压 (MABP)有明显上升 (P <0 .0 5 ,P <0 .0 1) ,死亡率下降 (P <0 .0 5 ,P <0 .0 1) ,循环血中TNF水平的升高受到明显的抑制 (P <0 .0 1)。同时 ,地塞米松预防和治疗能使内毒素休克动物血浆胰高血糖素、葡萄糖、乳酸和 β 葡萄糖醛酸酶 (β G)的升高得到明显改善 (P <0 .0 5 ,P <0 .0 1)。体外实验亦表明地塞米松预防能完全抑制肝Kupffer细胞释放TNF。结论 地塞米松对内毒素休克的防治效果与其直接抑制LPS诱导TNF的产生有密切关系。

s: 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.