Pichler L, Schramm W, Ulrich W, Varadi K, Schwarz H P
Department of Pharmacology and Toxicology, Immuno AG, Vienna, Austria.
Thromb Haemost. 1995 Feb;73(2):252-5.
We investigated the role of human protein C in an animal model of inflammatory hyperalgesia. Pain was induced by intraplantar injection of carrageenan (3 mg) into the hind paw of rats. The pain threshold was measured by exerting increasing amounts of pressure (in mmHg) on the paw until a struggle reaction was observed. Protein C (8-800 IU/kg) was administered intravenously immediately after carrageenan. Controls received either intraplantar injections of saline (100 microliters) instead of carrageenan or carrageenan alone. Effects on pain threshold were expressed in percent of the pretreatment value. Carrageenan alone lowered the mean pain threshold after 3 h to 33.2 +/- 2.2% of the pretreatment level. Addition of protein C resulted in a dose-dependent rise in pain threshold towards the level observed in control animals treated with saline instead of carrageenan (pain threshold after 800 IU/kg protein C = 62.9 +/- 2.3% of pretreatment level), demonstrating an antinociceptive effect. Protein C had no effect in animals not preconditioned with intraplantar carrageenan. Thus protein C clearly antagonized the inflammatory pain induced by carrageenan. The antinociceptive action of protein C was antagonized by injection of a monoclonal antibody against protein C, providing additional evidence that the effect was protein C-mediated.
我们在炎症性痛觉过敏动物模型中研究了人蛋白C的作用。通过将角叉菜胶（3毫克）足底注射到大鼠后爪来诱导疼痛。通过对爪子施加逐渐增加的压力（以毫米汞柱为单位）直至观察到挣扎反应来测量痛阈。在注射角叉菜胶后立即静脉注射蛋白C（8 - 800国际单位/千克）。对照组接受足底注射生理盐水（100微升）而非角叉菜胶或仅注射角叉菜胶。对痛阈的影响以预处理值的百分比表示。仅注射角叉菜胶后3小时，平均痛阈降至预处理水平的33.2±2.2%。添加蛋白C导致痛阈呈剂量依赖性升高，趋向于在用生理盐水而非角叉菜胶处理的对照动物中观察到的水平（800国际单位/千克蛋白C处理后的痛阈 = 预处理水平的62.9±2.3%），表明具有抗伤害感受作用。蛋白C对未预先用足底角叉菜胶处理的动物没有作用。因此，蛋白C明显拮抗了角叉菜胶诱导的炎性疼痛。注射抗蛋白C单克隆抗体可拮抗蛋白C的抗伤害感受作用，这进一步证明该作用是由蛋白C介导的。
