Blais C, Couture R, Drapeau G, Colman R W, Adam A
University of Montreal, Quebec, Canada.
Arthritis Rheum. 1997 Jul;40(7):1327-33. doi: 10.1002/1529-0131(199707)40:7<1327::AID-ART18>3.0.CO;2-B.
To investigate the pathophysiologic roles of endogenous bradykinin (BK) and des-Arg9-BK on local and systemic inflammatory responses in a rat model of acute arthritis induced by peptidoglycan-polysaccharide (PG-APS).
Female Lewis rats were injected intraperitoneally with PG-APS. Selective antagonists of B1 (Lys-[Leu8]-des-Arg9-BK) and B2 (Hoe 140) receptors were infused at 500 microg/kg and 5 mg/kg per day for 6 days, starting 3 days before induction of inflammation, with subcutaneous micro-osmotic pumps. The local inflammatory response was assessed by paw edema, joint swelling, and tissue content of BK and des-Arg9-BK. These peptides were measured by highly sensitive and specific chemiluminescent enzyme immunoassays. Systemic inflammatory reaction was evaluated by the hepatic concentration of the type 2 acute-phase protein T-kininogen.
PG-APS induced significant paw edema and joint swelling 24-72 hours after intraperitoneal injection. The maximal responses to PG-APS observed at 72 hours were significantly reduced (31-38%) by the combination of both B1 and B2 receptor antagonists at 5 mg/kg per day. PG-APS induced a significant increase of BK (up to 5.3-fold) and des-Arg9-BK (up to 4.1-fold) 72 hours after challenge. Liver T-kininogen content was increased by 5.3-, 7.7-, and 5.8-fold at 24, 48, and 72 hours, respectively, after PG-APS injection. At 24 hours, Hoe 140 and Lys-[Leu8]-des-Arg9-BK increased liver T-kininogen content by 43% and 45%, respectively, but they had no effect at 72 hours.
The results indicate that endogenous kinins are involved in local and systemic acute inflammatory responses, through both B1 and B2 kinin receptors, in the model of PG-APS-induced arthritis.
在肽聚糖 - 多糖（PG - APS）诱导的大鼠急性关节炎模型中，研究内源性缓激肽（BK）和去 - Arg9 - BK对局部和全身炎症反应的病理生理作用。
雌性Lewis大鼠腹腔注射PG - APS。从炎症诱导前3天开始，用皮下微渗透泵每天以500μg/kg和5mg/kg的剂量输注B1（Lys - [Leu8] - 去 - Arg9 - BK）和B2（Hoe 140）受体的选择性拮抗剂，持续6天。通过爪肿胀、关节肿胀以及BK和去 - Arg9 - BK的组织含量评估局部炎症反应。这些肽通过高度灵敏和特异的化学发光酶免疫测定法进行测量。通过2型急性期蛋白T - 激肽原的肝脏浓度评估全身炎症反应。
PG - APS腹腔注射后24 - 72小时引起显著的爪肿胀和关节肿胀。每天5mg/kg的B1和B2受体拮抗剂联合使用使72小时观察到的对PG - APS的最大反应显著降低（31 - 38%）。PG - APS攻击后72小时诱导BK（高达5.3倍）和去 - Arg9 - BK（高达4.1倍）显著增加。PG - APS注射后24、48和72小时，肝脏T - 激肽原含量分别增加5.3、7.7和5.8倍。在24小时时，Hoe 140和Lys - [Leu8] - 去 - Arg9 - BK分别使肝脏T - 激肽原含量增加43%和45%，但在72小时时它们没有作用。
结果表明，在PG - APS诱导的关节炎模型中，内源性激肽通过B1和B2激肽受体参与局部和全身急性炎症反应。
