Flores E A, Drabik M, Gauldie J, Blackburn G L, Dinarello C A, Bistrian B R
Cancer Research Institute, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215.
J Lab Clin Med. 1989 Feb;113(2):211-20.
This study examines the effect of a purified leukocyte-derived endogenous mediator (LEM) on protein metabolism during liver dysfunction and after sham surgery and the role of a nonsteroidal, antiinflammatory drug (indomethacin sodium trihydrate) in modifying this response. Febrile response, protein kinetics, urinary end products of protein metabolism, and plasma acute phase protein levels were studied in rats given a pyrogenic dose of LEM or saline solution, and these same indicators were studied after the administration of the same dose of LEM plus 2 mg/kg indomethacin 3 weeks after a portacaval shunt (PCS) or sham operation. In both surgical groups given LEM, a maximum of 1.1 degrees C fever was observed. LEM increased protein turnover and urinary excretion of nitrogen and urea in sham-operated rats but not in the PCS animals. Administration of indomethacin decreased the plasma oxidation of L[1-14C]leucine and prevented the increased excretion of total nitrogen and urea in sham-operated animals treated with LEM. PCS animals showed a constant excretion of nitrogen and urea independent of treatment. alpha 1-Acid glycoprotein levels increased significantly in sham-operated animals treated with LEM but not in the PCS group until indomethacin was added. The coadministration of LEM and indomethacin in shams also enhanced the levels of alpha 2-macroglobulin and alpha 1-acid glycoprotein over values found with LEM alone. These findings confirm the catabolic effect of LEM in normal animals and identify the essential role of the liver in the acute phase response. The data also suggest that indomethacin may modify the acute phase response by reducing plasma amino acid oxidation as well as enhancing the levels of some specific acute phase proteins.
本研究检测了一种纯化的白细胞源性内源性介质（LEM）对肝功能不全期间及假手术后蛋白质代谢的影响，以及一种非甾体抗炎药（三水合吲哚美辛钠）在改变这种反应中的作用。在给予致热剂量的LEM或盐溶液的大鼠中，研究了发热反应、蛋白质动力学、蛋白质代谢的尿终产物以及血浆急性期蛋白水平，并且在门腔分流术（PCS）或假手术后3周给予相同剂量的LEM加2mg/kg吲哚美辛后，对这些相同指标进行了研究。在给予LEM的两个手术组中，均观察到最高达1.1℃的发热。LEM增加了假手术大鼠的蛋白质周转率以及氮和尿素的尿排泄，但在PCS动物中未增加。吲哚美辛的给药降低了L-[1-¹⁴C]亮氨酸的血浆氧化，并防止了用LEM处理的假手术动物中总氮和尿素排泄的增加。PCS动物的氮和尿素排泄量恒定，与治疗无关。在接受LEM治疗的假手术动物中，α1-酸性糖蛋白水平显著升高，但在PCS组中，直到加入吲哚美辛后才升高。在假手术动物中同时给予LEM和吲哚美辛也使α2-巨球蛋白和α1-酸性糖蛋白水平高于单独使用LEM时的值。这些发现证实了LEM在正常动物中的分解代谢作用，并确定了肝脏在急性期反应中的重要作用。数据还表明，吲哚美辛可能通过减少血浆氨基酸氧化以及提高某些特定急性期蛋白的水平来改变急性期反应。
