Department of Physiology, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain.
J Physiol Pharmacol. 2012 Dec;63(6):649-59.
Cyclooxygenase-2-induction by inflammatory stimuli has been proposed as a mediator of inflammatory cachexia. We analyse whether cyclooxygenase-2 inhibition by meloxicam administration is able to modify the response of skeletal muscle to inflammation induced by lipopolysaccharide endotoxin (LPS). Male rats were injected with 1 mg kg(-1) LPS at 17:00 h and at 10:00 h the following day, and euthanized 4, 24 or 72 hours later. Atrogin-1, MuRF1, myogenic regulatory factors and cyclooxygenase-2 in the gastrocnemius were determined by real time-PCR (mRNA) and Western blot (protein). In a second experiment the effect of meloxicam administration (1 mg kg⁻¹) was analyzed. Meloxicam was administered either in a preventive manner, 1 hour before each endotoxin injection, or in a therapeutic manner, starting 2 hours after the second LPS injection and at 24 and 48 hours afterwards. There was a marked increase in MuRF1 mRNA (P<0.01) 4 hours after LPS, and in atrogin-1 mRNA 4 hours (P<0.01) and 24 hours (P<0.01) after LPS. Cyclooxygenase-2 was increased, whereas MyoD was decreased at 4, 24 and 72 h. Both types of meloxicam treatment blocked LPS-induced increase in atrogin-1. Preventive, but not therapeutic, meloxicam decreased myostatin (P<0.01) and increased Pax7 (P<0.01) and MyoD (P<0.05). Therapeutic meloxicam treatment decreased gastrocnemius myogenin. These data suggest that cyclooxygenase-2 inhibition by meloxicam administration can prevent the increase in atrogin-1 and the decrease in MyoD induced by LPS administration. However, prolonged therapeutic meloxicam treatment seems to be less effective, since it can inhibit myogenic regulatory factors.
环氧化酶-2 的诱导被认为是炎症性恶病质的一种介质。我们分析了通过给予美洛昔康抑制环氧化酶-2 是否能够改变内毒素脂多糖 (LPS) 诱导的炎症对骨骼肌的反应。雄性大鼠在 17:00 时和第二天 10:00 时分别注射 1 mg/kg LPS，并在 4、24 或 72 小时后安乐死。通过实时 PCR（mRNA）和 Western blot（蛋白）测定比目鱼肌中的肌萎缩蛋白 1（atrogin-1）、肌环指蛋白 1（MuRF1）、肌生成调节因子和环氧化酶-2。在第二个实验中分析了美洛昔康给药（1 mg/kg）的效果。美洛昔康以预防的方式给药，即在每次内毒素注射前 1 小时给药，或以治疗的方式给药，在第二次 LPS 注射后 2 小时开始给药，并在 24 和 48 小时后再次给药。在 LPS 后 4 小时 MuRF1 mRNA 显著增加（P<0.01），在 LPS 后 4 小时（P<0.01）和 24 小时（P<0.01）atrogin-1 mRNA 增加。环氧化酶-2 增加，而 MyoD 在 4、24 和 72 小时减少。两种类型的美洛昔康治疗均阻断 LPS 诱导的 atrogin-1 增加。预防治疗，而不是治疗，美洛昔康降低肌肉生长抑制素（P<0.01），增加 Pax7（P<0.01）和 MyoD（P<0.05）。治疗性美洛昔康治疗减少了比目鱼肌肌生成素。这些数据表明，通过给予美洛昔康抑制环氧化酶-2 可以防止 LPS 给药引起的 atrogin-1 增加和 MyoD 减少。然而，长期的治疗性美洛昔康治疗似乎效果较差，因为它可以抑制肌生成调节因子。
