Lazar G, Lazar G, Agarwal M K
Department of Surgery, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Circ Shock. 1992 Mar;36(3):180-4.
The survival rate in murine septic peritonitis was inversely proportional to the size of the needle used for cecal puncture following ligation below the ileocecal valve. The smaller, 20-gauge needle permitted 20% survival. Only 20% of the animals survived 24 hr after cecal puncture with a 20-gauge needle compared to 90% survival after 5 days if mice had been rendered tolerant to lipopolysaccharide (LPS) prior to the induction of peritonitis. A single intravenous injection of 1 mg RU 38486, concurrent with puncture with a 21-gauge needle, lowered survival to only 15% from the control level of 71%. This same dose of the antiglucocorticoid decreased the survival rate to only 35% from 90% in the tolerant group. Tolerance to the lethal effects of endotoxins, possibly responsible for resistance to septic peritonitis, was also abolished by the antiglucocorticoid. Just 1 mg RU 38486 lowered the survival rate to 5% if it was given with 600 micrograms LPS, which permitted 95% survival in LPS-tolerant mice and 60% survival in normal controls. Whereas both 1 mg RU 38486 and 100 micrograms dexamethasone, given alone, sensitized mice to septic peritonitis (15% and 30% survival, respectively), their combined effects neutralized each other, leading to 80% survival vs. 71% in the control group. Thus receptor-mediated glucocorticoid-dependent mechanisms appear important in the pathogenesis of both endotoxin and septic shock, albeit to varying degrees and in a seemingly contradictory manner.
在小鼠感染性腹膜炎中，存活率与在回盲瓣下方结扎后用于盲肠穿刺的针头大小成反比。较小的20号针头使存活率为20%。与在诱导腹膜炎前已对脂多糖（LPS）产生耐受的小鼠在盲肠穿刺5天后90%的存活率相比，用20号针头进行盲肠穿刺后仅20%的动物能存活24小时。在使用21号针头穿刺的同时静脉注射1毫克RU 38486，使存活率从对照组的71%降至仅15%。相同剂量的抗糖皮质激素使耐受组的存活率从90%降至仅35%。抗糖皮质激素也消除了对内毒素致死作用的耐受性，而内毒素可能是对感染性腹膜炎产生抗性的原因。如果在给予600微克LPS时同时给予1毫克RU 38486，存活率会降至5%，而600微克LPS能使LPS耐受小鼠的存活率达到95%，正常对照组的存活率为60%。单独给予1毫克RU 38486和100微克地塞米松都会使小鼠对感染性腹膜炎敏感（存活率分别为15%和30%），但它们的联合作用相互抵消，导致存活率为80%，而对照组为71%。因此，受体介导的糖皮质激素依赖性机制在 endotoxin 和感染性休克的发病机制中似乎都很重要，尽管程度不同且方式看似矛盾。
