Hall-Angerås M, Angerås U, Zamir O, Hasselgren P O, Fischer J E
Department of Surgery, University of Cincinnati Medical Center, Ohio.
Surgery. 1991 Apr;109(4):468-73.
The role of glucocorticoids in muscle catabolism during sepsis was tested with the glucocorticoid receptor antagonist RU 38486. Sepsis was induced in male Sprague-Dawley rats (40 to 60 gm) by cecal ligation and puncture (CLP). Other animals underwent sham operation. Two hours before CLP or sham operation, rats received RU 38486 (5 mg/kg) or a corresponding volume of vehicle by gavage. Sixteen hours after CLP or sham operation, protein synthesis rate was determined by measuring incorporation of 14C-phenylalanine into protein in incubated extensor digitorum longus muscles. Total and myofibrillar protein breakdown rates were determined by measuring net release of tyrosine and 3-methylhistidine, respectively. The protein synthesis rate was approximately 30% lower in rats with sepsis than in sham operated rats and was not affected by treatment with RU 38486. The total protein breakdown rate was increased by approximately 70% and myofibrillar protein degradation was increased more than fivefold in muscle from rats with sepsis. Treatment with RU 38486 resulted in a 28% reduction of total and a 44% reduction of myofibrillar protein breakdown in rats with sepsis but did not affect proteolysis in muscle from sham-operated animals. The results support a role of glucocorticoids in accelerated muscle proteolysis during sepsis. It is not clear whether glucocorticoids are the only required mediator or they interact with other substances to induce muscle protein breakdown during sepsis.
使用糖皮质激素受体拮抗剂RU 38486检测了糖皮质激素在脓毒症期间肌肉分解代谢中的作用。通过盲肠结扎和穿刺（CLP）在雄性Sprague-Dawley大鼠（40至60克）中诱导脓毒症。其他动物接受假手术。在CLP或假手术前两小时，大鼠通过灌胃接受RU 38486（5毫克/千克）或相应体积的载体。在CLP或假手术后16小时，通过测量14C-苯丙氨酸掺入孵育的趾长伸肌中的蛋白质来测定蛋白质合成率。分别通过测量酪氨酸和3-甲基组氨酸的净释放来测定总蛋白和肌原纤维蛋白的分解率。脓毒症大鼠的蛋白质合成率比假手术大鼠低约30%，且不受RU 38486治疗的影响。脓毒症大鼠肌肉中的总蛋白分解率增加了约70%，肌原纤维蛋白降解增加了五倍多。用RU 38486治疗可使脓毒症大鼠的总蛋白分解降低28%，肌原纤维蛋白分解降低44%，但不影响假手术动物肌肉中的蛋白水解。结果支持糖皮质激素在脓毒症期间加速肌肉蛋白水解中的作用。尚不清楚糖皮质激素是否是唯一必需的介质，或者它们是否与其他物质相互作用以在脓毒症期间诱导肌肉蛋白分解。
