Miller M L, Samuelson C O, Ward J R, Hiramoto R N
Infect Immun. 1979 Jul;25(1):337-44. doi: 10.1128/iai.25.1.337-344.1979.
Seven oral administrations of 6-sulfanilamidoindazole (6-SAI) to 10- to 12-month-old rats sensitized the animals to endotoxin, with dosages as small as 2.5 microgram causing death in 80% of animals. Endotoxin in a dosage of 3,000 microgram was not lethal for nonmedicated control animals. 6-SAI-treated 1-month-old rats were not as sensitive to endotoxin as aged animals. The sulfonamide-induced sensitivity to endotoxin could not be passively transferred and could not be explained by blockade of the reticuloendothelial system or impairment of endotoxin detoxification. 6-SAI administration was associated with both depletion of liver glycogen and lowering of blood glucose concentration without changes in blood lactic acid concentration. Disseminated intravascular coagulation is believed to be involved in the pathogenesis of shock and death as evidenced by: (i) concomitant decreases in plasma fibrinogen concentration and elevations in fibrin degradation products after endotoxin challenge; (ii) protection against lethal actions of endotoxin by pretreatment with heparin. Treatment of 6-SAI-medicated rats with glucocorticoids before endotoxin challenge protected the animals against lethal doses of endotoxin and prevented deposition of fibrin thrombi in the glomerular capillaries.
对10至12月龄大鼠口服七次6-磺胺氨基吲唑（6-SAI）可使动物对内毒素敏感，低至2.5微克的剂量可导致80%的动物死亡。3000微克剂量的内毒素对未用药的对照动物并不致命。用6-SAI处理的1月龄大鼠对内毒素的敏感性不如成年动物。磺胺类药物诱导的对内毒素的敏感性不能被动转移，也不能用网状内皮系统的阻断或内毒素解毒功能的损害来解释。给予6-SAI会导致肝糖原耗竭和血糖浓度降低，而血乳酸浓度无变化。弥散性血管内凝血被认为参与了休克和死亡的发病机制，证据如下：（i）内毒素攻击后血浆纤维蛋白原浓度同时降低，纤维蛋白降解产物升高；（ii）用肝素预处理可保护动物免受内毒素的致死作用。在内毒素攻击前用糖皮质激素治疗经6-SAI处理的大鼠，可保护动物免受致死剂量内毒素的影响，并防止纤维蛋白血栓在肾小球毛细血管中沉积。
