Kuttner R E, Schumer W
Circ Shock. 1984;13(3):233-40.
The lethality of endotoxin is greatly enhanced in lead-sensitized rats. Previous work showed that hepatic carbohydrate metabolism in lead-treated rats is perturbed by minute endotoxin doses [Fed Proc 41:1607, 1982]. These studies were extended to rats made tolerant to endotoxin by IV injection of lipopolysaccharide (50 micrograms/100 g body weight [BW]) 18 h before simultaneous treatment with lead acetate trihydrate (1.5 mg/100 g BW) and endotoxin (1.0 micrograms/100 g BW). Liver samples removed by freeze-clamping at 5 h from fasted young adult male rats were assayed for glycolytic intermediates. The tolerant rats generally showed smaller alterations in concentrations of metabolites than nontolerant comparison rats challenged with lead and endotoxin. However, phosphoenolpyruvate (PEP) levels were similarly elevated (80-90%) in both groups. The failure of the tolerance procedure to minimize or protect against hepatic PEP changes suggests that the enzymes forming or consuming this metabolite were particularly vulnerable to the action of an endotoxin-released mediator. The fact that some liver glycolytic intermediates remain markedly altered despite amelioration of the lethal effects of endotoxin by the tolerance procedure indicates the existence of independent mediators acting on carbohydrate metabolism in the endotoxic rats.
内毒素的致死性在铅致敏大鼠中大大增强。先前的研究表明，微量内毒素剂量会扰乱铅处理大鼠的肝脏碳水化合物代谢[《联邦程序》41:1607，1982]。这些研究扩展到通过在静脉注射脂多糖（50微克/100克体重[BW]）18小时后，同时用三水合醋酸铅（1.5毫克/100克体重）和内毒素（1.0微克/100克体重）处理而对内毒素产生耐受的大鼠。在禁食的成年雄性幼鼠5小时后通过冷冻钳夹取出肝脏样本，测定糖酵解中间产物。与用铅和内毒素攻击的非耐受对照大鼠相比，耐受大鼠的代谢物浓度变化通常较小。然而，两组中的磷酸烯醇丙酮酸（PEP）水平同样升高（80 - 90%）。耐受程序未能使肝脏PEP变化最小化或防止其变化，这表明形成或消耗这种代谢物的酶特别容易受到内毒素释放的介质的作用。尽管耐受程序减轻了内毒素的致死作用，但一些肝脏糖酵解中间产物仍有明显变化，这一事实表明在内毒素血症大鼠中存在独立作用于碳水化合物代谢的介质。
