Varisco P A, Péclat V, van Ness K, Bischof-Delaloye A, So A, Busso N
Laboratoire de Rhumatologie, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
Ann Rheum Dis. 2000 Oct;59(10):781-7. doi: 10.1136/ard.59.10.781.
To determine the effect of the thrombin inhibitor, hirudin, on the pathogenesis of murine antigen induced arthritis (AIA).
AIA was induced by intra-articular injection of methylated bovine serum albumin in the knee joints of previously immunised mice. Hirudin (injected subcutaneously 3 x 200 microg/mouse/day) was given over 13 days, starting three days before arthritis onset, and its anticoagulant effect monitored by clotting times. Arthritis severity was evaluated by technetium-99m ((99m)Tc) uptake in the knee joints and by histological scoring. In addition, intra-articular fibrin deposition was examined by immunohistochemistry, and synovial cytokine mRNA expression measured by RNase protection.
Joint inflammation, measured by (99m)Tc uptake, was significantly reduced in hirudin treated mice at days 7 and 10 after arthritis onset. Histologically, synovial thickness was markedly decreased in hirudin treated mice compared with untreated ones. By contrast, no difference in articular cartilage proteoglycan content was found between both groups. Intra-articular fibrin deposition and synovial interleukin 1beta mRNA levels, were slightly reduced ( approximately 20%) in arthritic joints from hirudin treated mice compared with untreated ones at day 10 of AIA.
Hirudin reduces joint inflammation associated with AIA by fibrin-dependent and independent mechanisms.
确定凝血酶抑制剂水蛭素对小鼠抗原诱导性关节炎（AIA）发病机制的影响。
通过在预先免疫的小鼠膝关节内注射甲基化牛血清白蛋白诱导AIA。从关节炎发作前三天开始，连续13天皮下注射水蛭素（3×200微克/小鼠/天），并通过凝血时间监测其抗凝效果。通过膝关节的99m锝（99mTc）摄取和组织学评分评估关节炎严重程度。此外，通过免疫组织化学检查关节内纤维蛋白沉积，并通过核糖核酸酶保护法测量滑膜细胞因子mRNA表达。
在关节炎发作后第7天和第10天，用水蛭素治疗的小鼠中，通过99mTc摄取测量的关节炎症明显减轻。组织学上，与未治疗的小鼠相比，水蛭素治疗的小鼠滑膜厚度明显降低。相比之下，两组之间关节软骨蛋白聚糖含量没有差异。在AIA第10天，与未治疗的小鼠相比，用水蛭素治疗的小鼠关节炎关节内的纤维蛋白沉积和滑膜白细胞介素1βmRNA水平略有降低（约20%）。
水蛭素通过纤维蛋白依赖性和非依赖性机制减轻与AIA相关的关节炎症。
