Tanaka J, Kono Y, Shimahara Y, Sato T, Jones R T, Cowley R A, Trump B F
Adv Shock Res. 1982;7:77-90.
Mechanisms of subcellular dysfunction of the liver in sepsis are still obscure. The present study investigates changes in oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following live Escherichia coli injection (E coli, Serotype: 0--18. A 1.25--1.5 X 10(9)/100 gm body wt inoculum of E coli bacteria was injected via the tail vein, causing a 100% mortality rate within 24 hours after injection. In order to determine alteration of liver mitochondrial membrane permeability, serum ornithine carbamoyltransferase activity was measured following E coli injection. This activity increased ten to 100-fold over that of controls with time following injection. However, the yield of liver mitochondria from treated rats, estimated by the amount of collected mitochondrial protein and the recovery rate of succinate dehydrogenase activity in the final mitochondrial suspensions, was not significantly different from that of controls. Mitochondrial oxidative phosphorylative activity measured using glutamate as a substrate was enhanced throughout all period to death (P less than 0.01 at three and six hours, P less than 0.05 in the fatal stage) and was associated with concomitant increases in respiratory control ratios. Similar results were obtained using beta-hydroxybutyrate as a substrate. This enhancement was accompanied by an increase in 2-4-dinitrophenol-stimulated ATPase activity (160% at three hours and 130% in the fatal stage). Calcium-induced stimulation of mitochondrial respiration as well as initial calcium uptake rate linked to respiration, using glutamate as a substrate, were higher in liver mitochondria from rats with E coli treatment than in those of controls throughout all periods (P less than 0.01 or less). These results suggest the coexistence of hyperfunctioning as well as deteriorated mitochondria following lethal treatment with E coli.
脓毒症时肝脏亚细胞功能障碍的机制仍不清楚。本研究调查了经尾静脉注射活的大肠杆菌（大肠杆菌，血清型：0-18。以1.25-1.5×10⁹/100克体重的接种量注射大肠杆菌，注射后24小时内死亡率达100%）后大鼠肝脏线粒体氧化磷酸化活性和钙诱导呼吸的变化。为了确定肝脏线粒体膜通透性的改变，在注射大肠杆菌后测定血清鸟氨酸氨基甲酰转移酶活性。该活性在注射后随时间比对照组增加了10至100倍。然而，通过收集的线粒体蛋白量和最终线粒体悬液中琥珀酸脱氢酶活性的回收率估算，处理组大鼠肝脏线粒体的产量与对照组无显著差异。以谷氨酸为底物测定的线粒体氧化磷酸化活性在直至死亡的所有时间段均增强（3小时和6小时时P<0.01，致死阶段P<0.05），并伴有呼吸控制率的相应增加。以β-羟基丁酸为底物也得到了类似结果。这种增强伴随着2,4-二硝基苯酚刺激的ATP酶活性增加（3小时时为160%，致死阶段为130%）。以谷氨酸为底物时，大肠杆菌处理组大鼠肝脏线粒体中钙诱导的线粒体呼吸刺激以及与呼吸相关的初始钙摄取率在所有时间段均高于对照组（P<0.01或更低）。这些结果表明，在大肠杆菌致死处理后，存在功能亢进以及功能恶化的线粒体。
