Corticosteroid treatment of experimental arthritis retards cartilage destruction as determined by histology and serum COMP

Corticosteroid treatment of experimental arthritis retards cartilage destruction as determined by histology and serum COMP
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DOI:
10.1093/rheumatology/keh073
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发表时间:
2004-04-01
期刊:
影响因子:
5.5
通讯作者:
Klareskog, L
Klareskog, L
中科院分区:
医学1区
文献类型:
--
作者:
Larsson, E;Harris, HE;Klareskog, L

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目标。检测血清软骨低聚基质蛋白(COMP)的变化是否与激素治疗的胶原性关节炎(CIA)动物软骨损伤的组织学分级有关。建立CIA的DA大鼠在关节炎评分超过1分后,每天一次腹腔注射皮质类固醇(倍他米松,0.1 mg/kg体重)或安慰剂(生理盐水)。整个研究过程继续进行。通过爪子的临床评分、血清COMP和纤维蛋白原的系列测定以及爪子的组织学分级来监测关节炎的进展。与安慰剂相比,皮质类固醇治疗减少了关节炎的临床症状(关节炎评分降低,第25天P&lt;0.01)。与安慰剂相比,皮质类固醇治疗也降低了纤维蛋白原水平(P&lt;0.01)。皮质类固醇治疗组的关节形态改变较轻(安慰剂组软骨评分中位数为4,皮质类固醇治疗组为0;P&lt;0.01)。在激素治疗的关节炎动物中,COMP水平在治疗期间保持不变,而在安慰剂治疗的大鼠中,COMP水平升高(P&lt;0.01)。免疫后第25天血清COMP水平与软骨破坏程度呈正相关(r=0.001.77,P<0.0 1)。对关节炎大鼠进行治疗的皮质类固醇可减轻关节组织学上的破坏,稳定的血清COMP水平反映了这一效果。
Objective. To examine if changes in serum cartilage oligomeric matrix protein (COMP) correlate with the development of cartilage damage, as measured by histological grading, in corticosteroid-treated animals with collagen-induced arthritis (CIA).Methods. DA rats with established CIA were treated with corticosteroids (betamethasone, 0.1 mg/kg body weight) or placebo (saline) intraperitoneally once daily after reaching an arthritis score exceeding 1. The treatment continued throughout the study. Arthritis progression was monitored by clinical scoring of paws, serial measurements of serum COMP and fibrinogen, and histological grading of paws.Results. Corticosteroid treatment reduced clinical signs of arthritis compared with placebo (arthritis score reduced, P < 0.01 at day 25). Corticosteroid treatment also reduced fibrinogen levels compared with placebo (P < 0.01). The morphological changes in the joint were less severe in the corticosteroid-treated animals (median cartilage score 4 in the placebo group, 0 in the corticosteroid-treated group; P < 0.01). The levels of COMP remained unchanged during treatment in the corticosteroid-treated arthritic animals, whereas an increase in levels of COMP was observed in rats treated with placebo (P < 0.01). There was a correlation between serum COMP and the extent of cartilage destruction at day 25 after immunization (r=0.77, P < 0.001).Conclusions. Corticosteroids given therapeutically to arthritic rats diminish joint destruction histologically, and stable serum COMP levels reflect this effect.