Ebata T, Kuttner R E, Apantaku F O, Schumer W
Adv Shock Res. 1983;9:275-82.
Peritonitis and endotoxemia produce similar derangements in carbohydrate metabolism, indicating a common mechanism of action. Endotoxin activates the complement chain by the alternate pathway with the release of chemical mediators. These mediators may be responsible for the changes occurring in hepatic metabolite pools during endotoxemia. This hypothesis was tested with FUT-175, a complement inhibitor, (2-(6-amidino)naphthyl-4-guanidinobenzoate 2HC1). Peritonitis was induced by cecal incision in fasted male rats. FUT-175 was infused in 5% dextrose at a dose of 0.1 mg/ml/h. Survival time was 12.1 +/- 2.3 h in the FUT-175 group and and 6.6 +/- 1.1 h without FUT-175. Three peritonitis groups received either 5% dextrose alone; FUT-175 2.5 mg/100 g by IP injection, or FUT-175 0.1 mg/ml/h by infusion. Liver was sampled at 5 h by freeze-clamping, and metabolites were assayed by UV spectrophotometry. Peritonitis caused 33% decrease in glucose-6-phosphate (G6P), a 2.5-fold increase in fructose diphosphate (FDP), and 3.5-fold increase in lactate. In FUT-175-injected rats, G6P was decreased by 20%, FDP increased only 50%, and lactate doubled. Phosphoenolpyruvate (PEP) levels were increased 30% above peritonitis values. The drug produced a partial normalization of liver metabolites. The data suggest that the anticomplement action prevented the release of potent mediators which otherwise cause physiological changes leading to the metabolic imbalance of septic shock.
腹膜炎和内毒素血症在碳水化合物代谢方面产生相似的紊乱，表明存在共同的作用机制。内毒素通过替代途径激活补体链并释放化学介质。这些介质可能是内毒素血症期间肝脏代谢物池发生变化的原因。用补体抑制剂FUT-175（2-（6-脒基）萘基-4-胍基苯甲酸2HCl）对这一假设进行了验证。通过对禁食雄性大鼠进行盲肠切开诱导腹膜炎。将FUT-175以0.1mg/ml/h的剂量注入5%葡萄糖溶液中。FUT-175组的存活时间为12.1±2.3小时，未使用FUT-175组的存活时间为6.6±1.1小时。三个腹膜炎组分别单独接受5%葡萄糖溶液；腹腔注射2.5mg/100g的FUT-175，或通过输注给予0.1mg/ml/h的FUT-175。在5小时时通过冷冻钳夹采集肝脏样本，并用紫外分光光度法测定代谢物。腹膜炎导致6-磷酸葡萄糖（G6P）减少33%，二磷酸果糖（FDP）增加2.5倍，乳酸增加3.5倍。在注射FUT-175的大鼠中，G6P减少20%，FDP仅增加50%，乳酸增加一倍。磷酸烯醇丙酮酸（PEP）水平比腹膜炎时的值升高30%。该药物使肝脏代谢物部分恢复正常。数据表明，抗补体作用阻止了强效介质的释放，否则这些介质会引起生理变化，导致感染性休克的代谢失衡。
