Blackburn W D, Loose L D, Heck L W, Chatham W W
Division of Clinical Immunology and Rheumatology, Birmingham Veterans Administration Medical Center, AL 35233.
Arthritis Rheum. 1991 Feb;34(2):211-6. doi: 10.1002/art.1780340213.
Neutrophils contain a collagenase that is stored in a latent form within the specific granule. With cellular activation, the latent enzyme is activated in association with the production of a variety of oxidants, including hypochlorous acid. We evaluated 4 nonsteroidal antiinflammatory drugs (NSAIDs) currently on the market and the new antiinflammatory/antirheumatic drug tenidap for their effects on the release of activated collagenase. In contrast to the 4 NSAIDs, tenidap profoundly inhibited the release of activated collagenase. This inhibition was predominantly due to interference with activation of the latent enzyme, rather than interference with enzyme release. The inhibition of collagenase activation was associated with a profound reduction in myeloperoxidase activity and in hypochlorous acid production. These observations demonstrate that tenidap has properties that set it apart from conventional NSAIDs and suggest that it may be a particularly useful agent in the treatment of inflammatory rheumatic disorders.
中性粒细胞含有一种胶原酶，它以潜伏形式储存在特异性颗粒中。随着细胞的激活，这种潜伏酶会与包括次氯酸在内的多种氧化剂的产生相关联而被激活。我们评估了目前市场上的4种非甾体抗炎药（NSAIDs）以及新型抗炎/抗风湿药替硝唑对活化胶原酶释放的影响。与这4种NSAIDs不同，替硝唑能显著抑制活化胶原酶的释放。这种抑制主要是由于对潜伏酶激活的干扰，而非对酶释放的干扰。胶原酶激活的抑制与髓过氧化物酶活性和次氯酸产生的显著降低相关。这些观察结果表明，替硝唑具有使其有别于传统NSAIDs的特性，并提示它可能是治疗炎性风湿性疾病的一种特别有用的药物。
