Zamir O, James J H, Hasselgren P O, Fischer J E
Department of Surgery, University of Cincinnati Medical Center, OH 45267-0558.
Metabolism. 1993 Sep;42(9):1190-4. doi: 10.1016/0026-0495(93)90279-w.
Sepsis and endotoxemia are associated with increased muscle protein breakdown and inhibited amino acid uptake. Glucocorticoids are important for the regulation of muscle protein breakdown in catabolic conditions; in contrast, the role of glucocorticoids in the regulation of muscle amino acid transport during sepsis or endotoxemia is not known. The present study was designed to test the role of glucocorticoids in the regulation of muscle amino acid uptake during endotoxemia. Amino acid transport, determined as uptake of 3H-alpha-aminoisobutyric acid (AIB) by incubated soleus muscles in vitro, was reduced by approximately 40% 2 hours after intraperitoneal (IP) injection of 10 micrograms/kg endotoxin in rats. Administration of 5 mg/kg of the glucocorticoid receptor antagonist RU 38486 2 hours before endotoxin injection did not affect the inhibition of amino acid uptake. In vitro addition of plasma from endotoxemic rats to incubated rat soleus muscles inhibited amino acid uptake by approximately 30%. This effect of endotoxic plasma also was noted when muscles were from rats that had been treated with RU 38486 and when RU 38486 was present in the incubation medium. Results confirm previous reports of reduced muscle amino acid transport during endotoxemia and of the presence of a circulating factor that inhibits muscle amino acid uptake in this condition. Data suggest that inhibited muscle amino acid transport during endotoxemia is not regulated by glucocorticoids.
脓毒症和内毒素血症与肌肉蛋白质分解增加及氨基酸摄取受抑制有关。糖皮质激素在分解代谢状态下对肌肉蛋白质分解的调节很重要;相比之下,糖皮质激素在脓毒症或内毒素血症期间对肌肉氨基酸转运的调节作用尚不清楚。本研究旨在测试糖皮质激素在内毒素血症期间对肌肉氨基酸摄取的调节作用。氨基酸转运通过体外孵育的比目鱼肌摄取³H-α-氨基异丁酸(AIB)来测定,在大鼠腹腔注射10微克/千克内毒素后2小时,氨基酸转运减少了约40%。在内毒素注射前2小时给予5毫克/千克的糖皮质激素受体拮抗剂RU 38486,并不影响氨基酸摄取的抑制作用。在内毒素血症大鼠的血浆体外添加到孵育的大鼠比目鱼肌中,可使氨基酸摄取抑制约30%。当肌肉来自用RU 38486处理过的大鼠以及孵育培养基中存在RU 38486时,内毒素血浆的这种作用也能观察到。结果证实了先前关于内毒素血症期间肌肉氨基酸转运减少以及存在一种循环因子在此情况下抑制肌肉氨基酸摄取的报道。数据表明,内毒素血症期间肌肉氨基酸转运受抑制并非由糖皮质激素调节。