Freund H R, James J H, LaFrance R, Gallon L S, Barcelli U O, Edwards L L, Joffe S N, Bjornson H S, Fischer J E
Arch Surg. 1986 Oct;121(10):1154-8. doi: 10.1001/archsurg.1986.01400100062012.
It has been recently suggested that increased muscle protein degradation during injury or infection is at least partially mediated by the increased production of prostaglandin E2 in muscle, and some have suggested that cyclooxygenase inhibitors might decrease protein loss in injured or septic patients. In these experiments, fractional synthesis rates of mixed muscle and liver protein and whole-body tyrosine flux were measured by constant intravenous infusion of tyrosine labeled with carbon 14 in 17 rats with sham operations and 15 severely septic rats with or without indomethacin treatment (20 mg/kg/d). Fractional synthesis rates in muscle and liver were decreased in late sepsis and were lowest in the septic group receiving indomethacin. Unlike the fractional synthesis rate, which was affected by indomethacin in septic rats only, tyrosine flux was significantly lower in indomethacin-treated rats with sham operations and those with sepsis. Although indomethacin reduced total-body protein breakdown during sepsis, it was also associated with lower plasma albumin levels and with decreased protein synthesis in muscle and liver at a time when the survival of the septic host may be dependent on its ability to produce new protein for a variety of vital functions. These results do not support the use of indomethacin in sepsis.
最近有人提出，在损伤或感染期间肌肉蛋白降解增加至少部分是由肌肉中前列腺素E2生成增加介导的，并且有人认为环氧化酶抑制剂可能会减少受伤或脓毒症患者的蛋白质损失。在这些实验中，通过对17只接受假手术的大鼠和15只患有严重脓毒症且接受或未接受吲哚美辛治疗（20mg/kg/d）的大鼠持续静脉输注碳14标记的酪氨酸，测量了混合肌肉和肝脏蛋白的分数合成率以及全身酪氨酸通量。脓毒症晚期肌肉和肝脏的分数合成率降低，在接受吲哚美辛治疗的脓毒症组中最低。与仅在脓毒症大鼠中受吲哚美辛影响的分数合成率不同，接受假手术且用吲哚美辛治疗的大鼠以及脓毒症大鼠的酪氨酸通量显著更低。尽管吲哚美辛在脓毒症期间降低了全身蛋白质分解，但在脓毒症宿主的存活可能依赖于其产生用于各种重要功能的新蛋白质的能力时，它还与较低的血浆白蛋白水平以及肌肉和肝脏中蛋白质合成减少有关。这些结果不支持在脓毒症中使用吲哚美辛。
