Disease Biology, Local Discovery Research Area CNS and Pain Control, AstraZeneca R&D Södertälje, Södertälje, Sweden.
Inflamm Res. 2010 Apr;59(4):315-21. doi: 10.1007/s00011-009-0107-6. Epub 2009 Oct 28.
The purpose of this study was to investigate if L(+)-lactate (lactate) can be used as a marker of progression of joint inflammation in comparison with a reference marker, prostaglandin E2 (PGE(2)), and to analyse implications for drug treatments.
The assessment of the inflammation time course and the treatment efficacy studies were performed on two occasions. At specific time points, synovial fluid was extracted from Sprague-Dawley rats (n = 87) challenged with either carrageenan (Cg) or Freund's complete adjuvant (FCA) or from six non-inflamed rats. Naproxen (7.5 or 30 micromol/kg) or rofecoxib (30 micromol/kg) was administered per os 2 h post Cg or at 48 h post FCA. Levels of PGE(2) and lactate were assessed either by immuno-assay or by colorimetric assay.
Increased levels of both markers were detected following Cg or FCA injection. Pharmacological treatments resulted in lower concentrations of PGE(2) whereas levels of lactate remained unaffected compared to the vehicle-treated group.
Our results suggest that lactate may be useful as an additional biomarker of inflammatory processes, especially for monitoring the non-cox-inhibitor sensitive cascade.
本研究旨在探讨 L(+)-乳酸(乳酸)是否可以作为关节炎症进展的标志物,与参考标志物前列腺素 E2(PGE(2))进行比较,并分析其对药物治疗的影响。
在两次不同的时间点进行了炎症时间进程的评估和治疗效果研究。在特定的时间点,从用角叉菜胶(Cg)或完全弗氏佐剂(FCA)刺激的 Sprague-Dawley 大鼠(n = 87)中提取滑液,或从 6 只非炎症大鼠中提取滑液。在 Cg 后 2 小时或 FCA 后 48 小时,经口给予萘普生(7.5 或 30 微摩尔/千克)或罗非昔布(30 微摩尔/千克)。通过免疫测定或比色法评估 PGE(2)和乳酸的水平。
在注射 Cg 或 FCA 后,两种标志物的水平均升高。与载体处理组相比,药物治疗导致 PGE(2)浓度降低,而乳酸水平保持不变。
我们的结果表明,乳酸可能是一种有用的炎症过程的附加生物标志物,特别是用于监测非 COX 抑制剂敏感级联。