INHIBITION OF PLASMA KALLIKREIN PREVENTS PEPTIDOGLYCAN-INDUCED ARTHRITIS IN THE LEWIS RAT
INHIBITION OF PLASMA KALLIKREIN PREVENTS PEPTIDOGLYCAN-INDUCED ARTHRITIS IN THE LEWIS RAT
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DOI：
10.1096/fasebj.9.5.7896018
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发表时间：
1995-03-01
期刊：
影响因子：
4.8
通讯作者：
COLMAN, RW
中科院分区：
文献类型：
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作者：
DELACADENA, RA;STADNICKI, A;COLMAN, RW
我们使用一种新的特异性血浆激肽释放酶抑制剂Bz-Pro-Phe-boroArg-OH（P8720）研究了先前显示的接触系统激活是否在肽聚糖多糖（PG-APS）诱导的大鼠急性炎症模型中起致病作用。第I组（对照组）既不接受PG-APS也不接受抑制剂。II组（疾病治疗组）腹腔注射（IF）PG-APS并口服P8720。第III组（未治疗疾病）接受PG-APS IP。第III组在49 h时贫血明显，但第I组和第II组中不存在贫血（P < 0.01）。与组III相比，组II的脾脏重量显著降低。在27 ~ 49 h，Ⅲ组急性关节炎逐渐发展，而Ⅱ组关节肿胀度降低61%（P < 0.0005）。我们观察到II组和III组的前激肽释放酶和因子XI显著下降（P < 0.01），但I组没有。在III组中观察到的高分子量激肽原功能水平的降低（P < 0.05）被II组中的P8720阻止。P8720可部分阻止T-激肽原和α 1-抑制剂3急性时相蛋白的变化。我们得出结论，导致关节炎和贫血的炎症反应，以及急性期反应，部分是由于接触激活，和特定的激肽释放酶抑制剂可能具有治疗潜力。
We investigate whether the previously shown contact system activation plays a pathogenetic role in a rat model of acute inflammation induced by peptido-glycan-polysaccharide (PG-APS) using a new specific plasma kallikrein inhibitor, Bz-Pro-Phe-boroArg-OH (P8720). Group I(control) received neither PG-APS nor inhibitor. Group II (disease-treated) received PG-APS intraperitoneally (IF) and P8720 orally. Group III(disease-untreated) received PG-APS IP. Anemia was evident at 49 h in group III but was not present (P < 0.01) in groups I and II. Spleen weight was significantly decreased in group II compared to group III. Acute arthritis progressively developed in group III from 27 to 49 h, but P8720 decreased the joint swelling in group II by 61% (P < 0.0005). We observed a significant fall in prekallikrein and factor XI (P < 0.01) in groups II and III but not in group I. The decrease in the functional levels of high molecular weight kininogen (P < 0.05) observed in group III were prevented by P8720 in group II. The changes in T-kininogen and alpha(1)-inhibitor 3 acute-phase proteins were partially prevented by P8720. We conclude that the inflammatory reactions leading to arthritis and anemia, as well as the acute-phase reaction, are due in part to contact activation, and that specific kallikrein inhibitors may have therapeutic potential.