Monophosphoryl lipid A protects against endotoxic shock via inhibiting neutrophil infiltration and preventing disseminated intravascular coagulation.

Circulatory shock Pub Date : 1994-07-01
Z Yao, P A Foster, G J Gross
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Abstract

The major objective of the present study was to determine the effects of a partial structure of the lipid A moiety of gram-negative lipopolysaccharide, monophosphoryl lipid A (MLA), on endotoxin-induced mortality and disseminated intravascular coagulation (DIC) in rats. A second objective was to examine the role of polymorphonuclear neutrophil invasion to visceral organs, including lung, liver, heart, and kidney in the pathogenesis of the compromised multiorgan function which occurs in endotoxic shock. Finally, a third aim was to determine if the potential protective effects of MLA might be mediated via inhibiting neutrophil invasion to various visceral organs. Male Sprague-Dawley rats (220-260 g) were fasted over night and used the following day. In control rats, endotoxin (S. abortus equi LPS, 15 mg/kg, i.v.) produced a 89% mortality at 48 hr following its administration, and gross pathological and laboratory signs of DIC at 3 hr after injection. The latter included increased serum fibrin(ogen) degradation products (FDP, 24.00 +/- 7.81 vs. 0 micrograms/ml, P < .05), prothrombin time (PT, 16.20 +/- 1.12 vs. 13.03 +/- 0.20 sec, P < .05), and activated partial thromboplastin time (APTT, 32.70 +/- 3.83 vs. 20.11 +/- 0.60 sec, P < .05), and decreased plasma fibrinogen (233.2 +/- 41.6 vs. 406.3 +/- 23.2 mg/dl, P < .05) as well as evidence of gross visceral hemorrhage. Pretreatment with MLA (5 mg/kg) for 24 hr produced a marked reduction in endotoxin-induced mortality at 48 hr (0% versus 89% in controls) and inhibited all of the manifestations of DIC produced by endotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

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单磷脂酰脂A通过抑制中性粒细胞浸润和防止弥散性血管内凝血来预防内源性休克。
本研究的主要目的是确定革兰氏阴性脂多糖单磷酰脂质a (MLA)的脂质a部分结构对内毒素诱导的大鼠死亡率和弥散性血管内凝血(DIC)的影响。第二个目的是研究多形核中性粒细胞侵入内脏器官,包括肺、肝、心和肾,在内毒素休克中发生的多器官功能受损的发病机制中的作用。最后,第三个目的是确定MLA的潜在保护作用是否可能通过抑制中性粒细胞对各种内脏器官的侵袭而介导。雄性Sprague-Dawley大鼠(220-260 g)禁食一夜,第二天使用。在对照大鼠中,内毒素(S. abortus equi LPS, 15 mg/kg,静脉注射)在给药后48小时导致89%的死亡率,在注射后3小时出现DIC的大体病理和实验室症状。后者包括血清纤维蛋白(原)降解产物(FDP, 24.00 +/- 7.81 vs. 0 μ g/ ml, P < 0.05),凝血酶原时间(PT, 16.20 +/- 1.12 vs. 13.03 +/- 0.20秒,P < 0.05),激活部分凝血活素时间(APTT, 32.70 +/- 3.83 vs. 20.11 +/- 0.60秒,P < 0.05),血浆纤维蛋白原降低(233.2 +/- 41.6 vs. 406.3 +/- 23.2 mg/dl, P < 0.05),以及内脏出血的证据。MLA (5mg /kg)预处理24小时可显著降低48小时内毒素引起的死亡率(0%,而对照组为89%),并抑制内毒素引起的DIC的所有表现。(摘要删节250字)
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