Hasselgren P O, Talamini M, LaFrance R, James J H, Peters J C, Fischer J E
Ann Surg. 1985 Nov;202(5):557-62. doi: 10.1097/00000658-198511000-00004.
The effect of indomethacin on protein degradation in skeletal muscle from septic rats was investigated. Sepsis was induced by cecal ligation and puncture (CLP). Control rats were sham-operated. Protein degradation rate was estimated by measuring release of tyrosine from incubated soleus (SOL) and extensor digitorum longus (EDL) muscles. Three experiments were performed. In the first experiment, indomethacin was administered subcutaneously (3 mg/kg) at the time of CLP and again after 3 hours. Control rats received corresponding volumes of solvent. Groups of rats were studied after 8 hours (early sepsis) or 16 hours (late sepsis). In the second experiment, the animals were pretreated 45 minutes before induction of sepsis with indomethacin (3 mg/kg) and again 3 hours after CLP and were studied during early sepsis. In the third experiment, indomethacin was added in vitro (3 microM) to incubated normal or septic muscle or to normal muscle incubated in the presence of plasma from septic animals, and release of prostaglandin E2 (PGE2) by incubated muscle was measured in addition to protein degradation. There was no mortality in early sepsis. Survival rate 16 hours after CLP was 8/16 (50%) in rats receiving control injections and 7/15 (47%) in indomethacin-treated rats (NS). Proteolytic rate in incubated EDL and SOL was increased by 20-25% during early sepsis and by 30-50% during late sepsis. The increased proteolytic rate was not affected by administration of indomethacin, neither in the first nor in the second experiment. When indomethacin was added in vitro, release of PGE2 by septic muscles and by normal muscles incubated in the presence of septic plasma was reduced by about 50%, but the increased proteolytic rate in these muscles was not affected. In normal muscle, neither release of PGE2 nor protein degradation was affected by indomethacin in vitro. The present results do not support a role for prostaglandins in the enhancement of muscle proteolysis during sepsis. Since neither survival rate nor protein breakdown was affected by indomethacin, recent suggestions to use this substance in the treatment of septic patients might be questioned.
研究了吲哚美辛对脓毒症大鼠骨骼肌蛋白质降解的影响。采用盲肠结扎和穿刺（CLP）诱导脓毒症。对照大鼠进行假手术。通过测量孵育的比目鱼肌（SOL）和趾长伸肌（EDL）中酪氨酸的释放来估计蛋白质降解率。进行了三个实验。在第一个实验中，在CLP时皮下注射吲哚美辛（3mg/kg），3小时后再次注射。对照大鼠接受相应体积的溶剂。在8小时（早期脓毒症）或16小时（晚期脓毒症）后研究大鼠组。在第二个实验中，在诱导脓毒症前45分钟用吲哚美辛（3mg/kg）预处理动物，CLP后3小时再次处理，并在早期脓毒症期间进行研究。在第三个实验中，在体外将吲哚美辛（3μM）添加到孵育的正常或脓毒症肌肉中，或添加到在脓毒症动物血浆存在下孵育的正常肌肉中，除了测量蛋白质降解外，还测量孵育肌肉中前列腺素E2（PGE2）的释放。早期脓毒症期间无死亡发生。接受对照注射的大鼠在CLP后16小时的存活率为8/16（50%），吲哚美辛治疗组为7/15（47%）（无显著性差异）。在早期脓毒症期间，孵育的EDL和SOL中的蛋白水解率增加20 - 25%，在晚期脓毒症期间增加30 - 50%。在第一个和第二个实验中，吲哚美辛的给药均未影响增加的蛋白水解率。当在体外添加吲哚美辛时，脓毒症肌肉以及在脓毒症血浆存在下孵育的正常肌肉中PGE2的释放减少约50%，但这些肌肉中增加的蛋白水解率未受影响。在正常肌肉中，体外吲哚美辛对PGE2的释放和蛋白质降解均无影响。目前的结果不支持前列腺素在脓毒症期间增强肌肉蛋白水解中起作用。由于吲哚美辛既不影响存活率也不影响蛋白质分解，最近关于在脓毒症患者治疗中使用该物质的建议可能值得质疑。
