Balis J U, Paterson J F, Shelley S A, Larson C H, Fareed J, Gerber L I
Lab Invest. 1979 Jan;40(1):55-65.
Liver changes and associated host responses were evaluated in four groups of male rats, weighing 300 +/- 20 gm., which received intravenous injection of 2.2 times 10(9) live Escherichia coli. This bolus was given either without additional treatment (group A) or prior to the following regimens: intramuscular injection of gentamicin sulfate, 5 mg. per kg. (group B); intravenous injection of methylprednisolone sodium succinate, 40 mg. per kg. (group C); and intramuscular injection of gentamicin immediately after methylprednisolone sodium succinate treatment (group D). Rats given injections of saline or methylprednisolone sodium succinate served as controls. Survival rates at 10 and 20 hours were 25 per cent and 4 per cent for group A; 44 per cent and 28 per cent for group B; 94 per cent and 70 per cent for group C; 98 per cent and 98 per cent for group D, respectively. In rats of groups A and B, killed at 1, 2, 4, and 6 hours, progressive liver changes included intravascular sequestration of rapidly degranulating leukocytes, fibrinous deposits, and platelet aggregates in sinusoids as well as in spaces of Disse adjacent to subendothelial collagen, and extensive Kupffer cell disruption in association with severe midzonal necrosis. These alterations were accompanied by progressive hypoglycemia and elevations of serum enzymes, glutamic pyruvic transaminase, lactate dehydrogenase, and glutamic oxaloacetic transaminase. Hematologic studies revealed that E. coli bacteremia results in rapid leukopenia and disseminated intravascular coagulation primarily due to activation of the intrinsic coagulation pathway. All above reactions were delayed and markedly reduced in rats treated with methylprednisolone sodium succinate. The results indicate that antibiotic treatment of lethal, Gram-negative bacteremia is effective only in conjunction with early steroid treatment. The protective effects of glucocorticoids on the liver microcirculation and polymorphonuclear leukocytes appear to play a basic role in preventing the early development of disseminated intravascular coagulation, hepatocellular necrosis, and associated major host responses, thereby attenuating lethality of gram-negative septic shock.
对四组体重为300±20克的雄性大鼠进行肝脏变化及相关宿主反应评估，这些大鼠静脉注射了2.2×10⁹ 活的大肠杆菌。这一大剂量注射在以下情况进行：要么不进行额外处理（A组），要么在以下方案之前进行：肌肉注射硫酸庆大霉素，每千克5毫克（B组）；静脉注射甲泼尼龙琥珀酸钠，每千克40毫克（C组）；以及在甲泼尼龙琥珀酸钠治疗后立即肌肉注射庆大霉素（D组）。注射生理盐水或甲泼尼龙琥珀酸钠的大鼠作为对照。A组在10小时和20小时的存活率分别为25%和4%；B组为44%和28%；C组为94%和70%；D组为98%和98%。在A组和B组于1、2、4和6小时处死的大鼠中，进行性肝脏变化包括快速脱颗粒白细胞的血管内隔离、纤维蛋白沉积、窦状隙以及与内皮下胶原相邻的狄氏间隙中的血小板聚集，以及与严重中区坏死相关的广泛库普弗细胞破坏。这些改变伴随着进行性低血糖以及血清酶谷氨酸丙酮酸转氨酶、乳酸脱氢酶和谷氨酸草酰乙酸转氨酶的升高。血液学研究表明，大肠杆菌菌血症主要由于内源性凝血途径的激活导致快速白细胞减少和弥散性血管内凝血。在用甲泼尼龙琥珀酸钠治疗的大鼠中，所有上述反应均延迟且明显减轻。结果表明，对抗致命性革兰氏阴性菌血症的抗生素治疗仅与早期类固醇治疗联合才有效。糖皮质激素对肝脏微循环和多形核白细胞的保护作用似乎在预防弥散性血管内凝血、肝细胞坏死及相关主要宿主反应的早期发展中起基本作用，从而减轻革兰氏阴性脓毒症休克的致死性。
