Vargaftig B B, Lefort J, Giroux E L
Agents Actions. 1976 Sep;6(5):627-35. doi: 10.1007/BF01971582.
Collagenase from Clostridium histolyticum induced haemorrhages when applied to the surface of dog lung; it exerted a similar effect on mouse lung when injected intrathoracically. Injected into rat paws, bacterial collagenase induced haemorrhage and oedema. Effects of collagenase were prevented by several procedures that inhibit collagenolytic activity (heating at various temperatures and incubation with metal-complexing agents such as EDTA, penicillamine and dithiothreitol). Protein protease inhibitors, dexamethasone and standard acidic anti-inflammatory drugs had only a slight or no effect on collagenase-induced haemorrhages; dexamethasone and acidic anti-inflammatory drugs blocked collagenase-induced oedema. Inhibition of endogenous kinin-releasing mechanisms by administration of hexadimethrine, a recognized inhibitor of the activation of clotting Factor XII, and depletion of kininogen by administration of carrageenin blocked collagenase-induced oedema. Collagenase did not increase permeability of rat skin vessels, nor did it release potential inflammatory mediators, such as bradykinin or prostaglandins, from plasma or platelets. Bacterial collagenase-induced haemorrhage presumably resulted from enzymatic destruction of membranous structures; at least a portion of the inflammatory response may be due to activation of a kinin-like system.
溶组织梭菌胶原酶涂抹于犬肺表面时会引发出血；经胸腔内注射时，它对小鼠肺也有类似作用。注射到大鼠爪中，细菌胶原酶会引发出血和水肿。胶原酶的作用可通过多种抑制胶原分解活性的方法来预防（在不同温度下加热以及与金属螯合剂如乙二胺四乙酸、青霉胺和二硫苏糖醇一起孵育）。蛋白质蛋白酶抑制剂、地塞米松和标准酸性抗炎药对胶原酶引发的出血仅有轻微作用或无作用；地塞米松和酸性抗炎药可阻止胶原酶引发的水肿。通过给予已确定的凝血因子XII激活抑制剂六甲双铵抑制内源性激肽释放机制，以及通过给予角叉菜胶消耗激肽原，可阻止胶原酶引发的水肿。胶原酶不会增加大鼠皮肤血管的通透性，也不会从血浆或血小板中释放潜在的炎症介质，如缓激肽或前列腺素。细菌胶原酶引发的出血大概是由于膜结构的酶促破坏；至少部分炎症反应可能是由于类激肽系统的激活。
