急性肝衰竭时肠源性内毒素血症对肝脏能量代谢的影响

目的:研究急性肝衰竭时肠源性内毒素血症对肝脏能量代谢的影响。方法:以硫代乙酰胺(TAA)染毒建立急性肝损伤大鼠模型;应用酶荧光法测定动脉血酮体(乙酰乙酸、β-羟基丁酸)浓度及肝细胞线粒体ATP含量;采用结肠切除术并观察血浆内毒素水平与血清丙氨酸氨基移换酶(ALT)活性的变化。结果:TAA组大鼠血浆内毒素水平与血清ALT活性均显著高于正常对照组(P＜0.01),动脉血酮体比(AKBR)降至0.4以下,动脉血中总酮体浓度显著低于正常对照组(P＜0.01)。切除结肠的TAA染毒组大鼠未发生内毒素血症,肝细胞线粒体ATP含量显著高于TAA组(P＜0.01),血清ALT活性虽高于正常对照组(P＜0.05),但显著低于TAA组(P＜0.01)。结论:肠源性内毒素血症可损伤肝脏能量代谢,使肝脏代谢和功能发生严重障碍,在急性肝衰竭的发生过程中具有关键性作用。

Effect of intestinal endotoxemia on hepatic energy metabolism in acute liver failure

AIM:To study the effect of intestinal endotoxemia(IETM) on hepatic energy metabolism in acute liver failure. METHODS:Intoxication by thioacetamide (TAA) was used to establish rat model of acute liver injury.Ketone body(acetoacetate and β-hydroxybutyrate) in arterial blood and ATP content of hepatocellular mitochondria were determined by using enzymatic fluorimetric micromethod.Colectomy was adopted in observing the changes in plasma endotoxin content and serum alanine aminotransferase (ALT) activity. RESULTS:In the TAA group,plasma endotoxin content and serum ALT activity were all significantly higher than those in the control group(P＜0.01),arterial ketone body ratio of acetoacetate to β-hydroxybutyrate (AKBR) decreased below 0.4,total ketone body in arterial blood was significantly lower than that in the control group(P＜0.01).In the TAA+colectomy group,there was no endotoxemia to be found,ATP content of hepatocellular mitochondria was significantly higher than that in the TAA group(P＜0.01), though serum ALT activity was higher than that in the control group(P＜0.05),but significantly lower than that in the TAA group(P＜0.01). CONCLUSION:IETM played a key role in the occurrence of acute liver failure,hepatic dysfunction might be caused by IETM through damaging hepatic energy metabolism.