糖皮质激素受体减少对内毒素血症并发多脏器损伤的病因学作用

The effect of depletion of glucocorticoid receptor in the production of multiple organ failure during endotoxemia

我们在阻断大鼠糖皮质激素受体(GR)基础上复制了内毒素血症模型,观察到大鼠血清酸性磷酸酶活性、磷脂酶 A_2活性和脂质过氧化物含量均比 GR 不阻断的单纯内毒索血症时显著升高,并出现多脏器的病理损害。提示严重创伤或休克后 GR 减少对多器官功能衰竭具有发病学意义.

Endotoxin(20 mg/kg B.W.)was injected intravenously to control(n=12)and gluco- corticoid receptor(GR)depletion rat model(n=13,in which more than 80 percent of GR were blocked with a potent GR antagonist RU486).Four hours after injection of endotoxin,the changes in serum acid phosphatase(ACP)activity,phospholipase A_2(PLA_2)activity and li- pid peroxide(LPO)level were determined.The results showed that all of the indices were in- creased in the control rats after endotoxin injection(ACP 17.6±1.9U/dL,PLA_2 325.6±99.1 U,and LPO 6.0±0.4 nmol MDA·ml^(-1)),but they were increased to even higher levels in the rats injected with both RU486 and endotoxin(ACP 30.1±7.6U/dL,PLA_2 633.7± 70.6U,and LPO 8.2±1.1 nmol MDP·ml^(-1)).Furthermore,the lafter presented multiple organ damage pathologically.These results suggested that the glucocortieoid insufficiency caused by the decrease of GR after severe trauma or shock may exacerbate the damage of endotoxin to the organs,so much so that glucocorticoid insufficiency might result in multiple organ failure.This article also discussed problem of glucocortcoid treatment.