Fukumoto Koji, Pierro Agostino, Spitz Lewis, Eaton Simon
Department of Paediatric Surgery, Institute of Child Health, London, England.
J Pediatr Surg. 2003 May;38(5):690-3. doi: 10.1016/jpsu.2003.50184.
The aim was to determine the effects of early and late endotoxemia on neonatal cardiac and renal mitochondrial energetics.
Suckling rats received intraperitoneal 300 microgram/kg lipopolysaccharide; controls received saline. Heart and kidney mitochondria were isolated after 2 hours (early) or 6 hours (late sepsis). State 3 (maximum mitochondrial flux) and 4 O(2) consumption and complex I activity were measured. Results, expressed as mean +/- SEM normalized to citrate synthase (CS), were compared using paired t tests.
Mortality rate was zero within 2 hours, 2.7% between 2 and 6 hours of endotoxemia, and 100% 6 to 8 hours; therefore, we consider that 2 hours and 6 hours represent early and late endotoxemia, respectively. Endotoxic heart mitochondria had unaltered O(2) consumption at 2 hours but significantly decreased state 3 after 6 hours, resulting in significantly decreased respiratory control ratio. Complex I activity, which could affect O(2) consumption, was decreased significantly at 6 hours (9.8 +/- 0.6 mU/U CS; n = 15) versus controls (11.3 +/- 0.8, n = 15; P =.04), but not at 2 hours. There were no differences in these measurements at either 2 hours or 6 hours in kidney mitochondria.
The respiratory chain is affected late in endotoxemia. Neither early nor late endotoxemia affects oxidative function of kidney mitochondria.
本研究旨在确定早期和晚期内毒素血症对新生大鼠心脏和肾脏线粒体能量代谢的影响。
给乳鼠腹腔注射300微克/千克脂多糖；对照组注射生理盐水。在2小时（早期）或6小时（晚期脓毒症）后分离心脏和肾脏线粒体。测量状态3（最大线粒体通量）、状态4氧气消耗以及复合物I活性。结果以相对于柠檬酸合酶（CS）的平均值±标准误表示，采用配对t检验进行比较。
2小时内死亡率为零，内毒素血症2至6小时之间死亡率为2.7%，6至8小时死亡率为100%；因此，我们认为2小时和6小时分别代表早期和晚期内毒素血症。内毒素血症早期（2小时）时，心脏线粒体的氧气消耗未改变，但6小时后状态3显著降低，导致呼吸控制率显著下降。可影响氧气消耗的复合物I活性在6小时时显著降低（9.8±0.6毫微摩尔/微克CS；n = 15），而对照组为（11.3±0.8，n = 15；P =.04），但在2小时时无差异。肾脏线粒体在2小时或6小时时这些测量值均无差异。
内毒素血症后期呼吸链受到影响。早期和晚期内毒素血症均不影响肾脏线粒体的氧化功能。
