Murata A, Toda H, Uda K, Hayashida H, Kato T, Nakagawa H, Yokoyama S, Morishita H, Yamakawa T, Hirose J
Department of Surgery II, Osaka University Medical School, Japan.
Inflammation. 1994 Aug;18(4):337-47. doi: 10.1007/BF01534432.
Severe inflammatory responses after major surgeries, trauma, and infection develop multiple organ dysfunction. In the mechanisms of the pathogenesis of these responses, activated neutrophils are thought to be important in terms of their ability to produce various kinds of proteinases, which can degrade various proteins constructing human tissues. Among their proteinases, neutrophil elastase is the strongest serine proteinase secreted from activated neutrophils. Thus, we examined in this study the inhibitory effect and therapeutic efficacy of newly produced recombinant human Kunitz-type proteinase inhibitor (R-020), which coded the second domain of human urinary trypsin inhibitor. R-020 was effective in significantly improving the survival rate after induction of the rat lethal peritonitis model (cecal ligation and puncture-induced septic shock model). We suggest that various serine proteinases are implicated in the pathogenesis of neutrophil-related multiple organ failure and that recombinant human Kunitz-type proteinase inhibitor might be effective in the treatment of these kinds of organ dysfunction.
大手术、创伤和感染后的严重炎症反应会引发多器官功能障碍。在这些反应的发病机制中，活化的中性粒细胞被认为因其能够产生各种蛋白酶而具有重要作用，这些蛋白酶可降解构成人体组织的各种蛋白质。在它们产生的蛋白酶中，中性粒细胞弹性蛋白酶是活化的中性粒细胞分泌的最强丝氨酸蛋白酶。因此，我们在本研究中检测了新产生的重组人库尼茨型蛋白酶抑制剂（R-020）的抑制作用和治疗效果，该抑制剂编码人尿胰蛋白酶抑制剂的第二个结构域。R-020能有效显著提高大鼠致死性腹膜炎模型（盲肠结扎和穿刺诱导的脓毒性休克模型）诱导后的存活率。我们认为，各种丝氨酸蛋白酶与中性粒细胞相关的多器官功能衰竭的发病机制有关，重组人库尼茨型蛋白酶抑制剂可能对治疗这类器官功能障碍有效。
