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抗关节炎化合物对大鼠II型胶原诱导性关节炎的影响。

Effects of antiarthritic compounds on type II collagen-induced arthritis in rats.

作者信息

Probert A W, Schrier D J, Gilbertsen R B

出版信息

Arch Int Pharmacodyn Ther. 1984 May;269(1):167-76.

PMID:6466005
Abstract

The therapeutic effects of a variety of agents on established lesions of type II collagen arthritis in rats were tested. Drug activity was determined using an Arthritic Index, which consisted of a rank score ranging from 0 to 8 (0 to 4 in each hind paw) based on hind paw swelling and redness, and by measuring titers of antibody to type II collagen. Four of five non-steroidal antiinflammatory drugs (NSAIDs), phenylbutazone, benoxaprofen, indomethacin and isoxicam, reduced swelling. Of the NSAIDs, only acetylsalicylic acid was inactive. None of these drugs reduced levels of antibody to type II collagen as determined by an ELISA procedure. One of two immunosuppressive drugs, cyclophosphamide, and a steroid, hydrocortisone acetate, significantly inhibited hind paw inflammation. The other immunosuppressive, azathioprine, did not significantly reduce swelling. Also, cyclophosphamide lowered levels of antibody to type II collagen. Five antirheumatic agents, auranofin, levamisole, D-penicillamine, chloroquine and aurothioglucose, were tested and none inhibited the disease process. Of these five, only auranofin inhibited antibody titer to type II collagen. In conclusion, although rat type II collagen arthritis did not detect standard antirheumatic drugs, this model detected the activity of several standard NSAIDs, an immunosuppressive, and a steroid. In addition, the level of antibody to type II collagen was neither a selective nor sensitive indicator of the efficacy of standard antiarthritic agents.

摘要

测试了多种药物对大鼠已形成的II型胶原性关节炎损伤的治疗效果。使用关节炎指数来确定药物活性,该指数由基于后爪肿胀和发红的0至8级评分(每只后爪0至4级)组成,并通过测量抗II型胶原抗体的滴度来确定。五种非甾体抗炎药(NSAIDs)中的四种,即保泰松、苯恶洛芬、吲哚美辛和异恶酰胺,减轻了肿胀。在这些NSAIDs中,只有乙酰水杨酸没有活性。通过酶联免疫吸附测定法(ELISA)测定,这些药物均未降低抗II型胶原抗体的水平。两种免疫抑制药物中的一种,即环磷酰胺,以及一种类固醇,即醋酸氢化可的松,显著抑制了后爪炎症。另一种免疫抑制剂硫唑嘌呤没有显著减轻肿胀。此外,环磷酰胺降低了抗II型胶原抗体的水平。测试了五种抗风湿药物,即金诺芬、左旋咪唑、D-青霉胺、氯喹和金硫葡萄糖,均未抑制疾病进程。在这五种药物中,只有金诺芬抑制了抗II型胶原抗体的滴度。总之,尽管大鼠II型胶原性关节炎未检测到标准抗风湿药物的活性,但该模型检测到了几种标准NSAIDs、一种免疫抑制剂和一种类固醇的活性。此外,抗II型胶原抗体水平既不是标准抗关节炎药物疗效的选择性指标,也不是敏感指标。

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