Doughty J R, Goldberg R L, Schenkelaars E J, Singh H N, Peppard J, Haston W, Blancuzzi V J, Di Pasquale G
Research Department, CIBA-GEIGY Corporation, Summit, NJ 07901.
Agents Actions. 1991 Sep;34(1-2):129-31. doi: 10.1007/BF01993257.
Rat adjuvant arthritis (AA) was used as a model to evaluate several blood markers as possible predictive indicators of drug efficacy. AA was induced in Sprague-Dawley rats by the injection of complete Freund's adjuvant into the right hind foot pad. The rats were dosed p.o. from day 18 to day 31 with levamisole (10 mg/kg), indomethacin (1 mg/kg), diclofenac sodium (0.5 & 1 mg/kg), and prinomide (10 & 20 mg/kg). Disease severity was assessed by paw circumference on day 31. The following blood markers were analyzed: hyaluronate by ELISA, prostaglandin E2 by RIA, ESR by micro-dispette, total PMN by Technicon H-1, and albumin by BCG dye. Blood marker correlation (r) to disease severity was: hyaluronate (0.71), prostaglandin E2 (0.58), ESR (0.52), PMN (0.58), and albumin (-0.71). The relative rank order of drug efficacy (indomethacin, diclofenac sodium, and prinomide) did not differ using the change in paw circumference (day 31-day 17) or blood markers. Levamisole exacerbated the disease as measured by all the above parameters. Thus, these blood markers provide additional information for the statistical evaluation of drugs in rat adjuvant arthritis.
大鼠佐剂性关节炎（AA）被用作模型，以评估几种血液标志物作为药物疗效的可能预测指标。通过将完全弗氏佐剂注射到Sprague-Dawley大鼠的右后足垫诱导AA。从第18天到第31天，大鼠口服给予左旋咪唑（10 mg/kg）、吲哚美辛（1 mg/kg）、双氯芬酸钠（0.5和1 mg/kg）和普立酰胺（10和20 mg/kg）。在第31天通过爪周长评估疾病严重程度。分析了以下血液标志物：通过ELISA检测透明质酸盐，通过RIA检测前列腺素E2，通过微量移液器检测血沉，通过Technicon H-1检测总中性粒细胞，通过BCG染料检测白蛋白。血液标志物与疾病严重程度的相关性（r）为：透明质酸盐（0.71）、前列腺素E2（0.58）、血沉（0.52）、中性粒细胞（0.58）和白蛋白（-0.71）。使用爪周长变化（第31天-第17天）或血液标志物时，药物疗效（吲哚美辛、双氯芬酸钠和普立酰胺）的相对排名顺序没有差异。通过上述所有参数测量，左旋咪唑会加重疾病。因此，这些血液标志物为大鼠佐剂性关节炎中药物的统计学评估提供了额外信息。
