Colman R W, Stadnicki A, Kettner C A, Adam A A, DeLa Cadena R A, Sartor R B
Sol Sherry Thrombosis Research Center, USA.
Proc Assoc Am Physicians. 1997 Jan;109(1):10-22.
We have developed models of acute and chronic inflammatory arthritis and enterocolitis using peptidoglycan-polysaccharide injected intraperitoneally or subserosally (intramurally) into the distal ileum and cecum. Acute inflammation occurs in both Buffalo and Lewis rats, characterized by inflammation of the injected areas of the intestine. However, only the genetically susceptible Lewis rat develops chronic synovitis and joint erosion or adhesions and granulomatous enterocolitis. In the Lewis rat but not the Buffalo rat, these changes are accompanied by a decrease in plasma prekallikrein and high-molecular-weight kininogen, reflecting activation of the kallikrein-kinin system. Pretreatment with a specific plasma kallikrein inhibitor modulates the acute and chronic arthritis. The same inhibitor partially abrogates the acute changes characteristic of enterocolitis, and preliminary data suggest similar results in the chronic model. The results of these studies indicate that the kallikrein-kinin system plays an important role in arthritis and enterocolitis induced by bacterial products and that kallikrein inhibitors are potential therapeutic agents for inflammatory arthritis and inflammatory bowel disease.
我们通过将肽聚糖 - 多糖经腹腔内或浆膜下（壁内）注射到回肠末端和盲肠，建立了急性和慢性炎症性关节炎及小肠结肠炎的模型。急性炎症在布法罗大鼠和刘易斯大鼠中均会发生，其特征为注射部位的肠道出现炎症。然而，只有基因易感性的刘易斯大鼠会发展为慢性滑膜炎、关节侵蚀或粘连以及肉芽肿性小肠结肠炎。在刘易斯大鼠而非布法罗大鼠中，这些变化伴随着血浆前激肽释放酶和高分子量激肽原的减少，这反映了激肽释放酶 - 激肽系统的激活。用特定的血浆激肽释放酶抑制剂进行预处理可调节急性和慢性关节炎。相同的抑制剂部分消除了小肠结肠炎的急性特征变化，初步数据表明在慢性模型中也有类似结果。这些研究结果表明，激肽释放酶 - 激肽系统在细菌产物诱导的关节炎和小肠结肠炎中起重要作用，并且激肽释放酶抑制剂是炎性关节炎和炎性肠病的潜在治疗药物。
