Spitzer J J, Bagby G J, Meszaros K, Lang C H
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Prog Clin Biol Res. 1989;286:145-65.
Based on our data, we envisage the following sequence of events to occur after the administration of a moderately severe dose of endotoxin: Sympathetic stimulation due to hypotension, and possibly other factors, increases plasma concentration of catecholamines. Increased hepatic phosphorylase a activity depletes existing glycogen stores and causes transient hyperglycemia. Lactate release from skeletal muscle is also enhanced, due to the more sustained activation of muscle phosphorylase a and increased uptake of plasma glucose. Stimulation of the immunologically active tissues by endotoxin with the participation of mononuclear phagocytes and TNF results in elevated glycolysis in these tissues as well, thus further enhancing the hyperlactacidemia. The increased precursor concentration and their delivery to the liver stimulate gluconeogenesis, in spite of endotoxin-induced suppression of PEPCK activity. Thus, an elevated precursor supply accelerates gluconeogenesis which is primarily responsible for the increased glucose Ra when hepatic glycogen stores are depleted. It appears that both an increase in blood lactate and catecholamines are important in maintaining the increased gluconeogenesis. This is illustrated schematically in Fig. 4. We postulate that in the fasted nutritionally nonsupported rat, endotoxin enhances glucose utilization in immunologically active tissues as well as in muscle. The presence of catecholamines and the glycolytically produced lactate stimulates gluconeogenesis. These events support the mounting of an effective immune response and aid the body to maintain the immune response by conserving glucose carbon.
根据我们的数据，我们设想在给予中等严重剂量的内毒素后会发生以下一系列事件：由于低血压以及可能的其他因素导致的交感神经刺激会增加血浆儿茶酚胺浓度。肝磷酸化酶a活性增加会耗尽现有的糖原储备并导致短暂的高血糖。骨骼肌中乳酸的释放也会增强，这是由于肌肉磷酸化酶a的持续激活以及血浆葡萄糖摄取增加所致。内毒素在单核吞噬细胞和肿瘤坏死因子的参与下刺激免疫活性组织，也会导致这些组织中的糖酵解增加，从而进一步加剧高乳酸血症。尽管内毒素会抑制磷酸烯醇丙酮酸羧激酶（PEPCK）的活性，但前体浓度的增加及其向肝脏的输送会刺激糖异生。因此，当肝糖原储备耗尽时，前体供应的增加会加速糖异生，这主要是导致葡萄糖输注率（Ra）增加的原因。似乎血液中乳酸和儿茶酚胺的增加对于维持糖异生的增加都很重要。图4以示意图的形式说明了这一点。我们推测，在禁食且无营养支持的大鼠中，内毒素会增强免疫活性组织以及肌肉中的葡萄糖利用。儿茶酚胺的存在以及糖酵解产生的乳酸会刺激糖异生。这些事件有助于增强有效的免疫反应，并通过保存葡萄糖碳来帮助身体维持免疫反应。
