Kawabata Kazuhito, Hagio Tetsuya, Matsuoka Shozo
Discovery Research Laboratory II, Minase Research Institute, Ono Pharmaceutical Co., Ltd., Mishima, Osaka, Japan.
Nihon Yakurigaku Zasshi. 2003 Aug;122(2):151-60. doi: 10.1254/fpj.122.151.
Imbalance between neutrophil elastase (NE) and its endogenous protease inhibitors has been considered to be one of possible mechanisms by which NE causes lung tissue destruction. It has been shown that the amount and/or activity of NE is increased in blood and bronchoalveolar lavage fluid in patients with acute lung injury. Accordingly, animals undergoing acute lung injury have increased NE activity such as in blood and bronchoalveolar lavage fluid. Sivelestat sodium hydrate (Sivelestat) is a synthetic inhibitor of NE with highly specificity to NE. Many studies have indicated that Sivelestat treatment improves inflammatory and edematous changes of lungs and survival as well as increased NE activity in several animal models of acute lung injury. Clinical studies have demonstrated that Sivelestat improves this injury that is associated with systemic inflammatory response syndrome. As compared with endogenous protease inhibitors that have high molecular mass, Sivelestat, a synthetic and low molecular weight elastase inhibitor, may be delivered to the inflammatory sites more easily and effectively and is considred to improve typical symptoms of acute lung injury. Clinical use of Sivelestat would further clarify the usefulness of this compound in clinical acute lung injury.
中性粒细胞弹性蛋白酶（NE）与其内源性蛋白酶抑制剂之间的失衡被认为是NE导致肺组织破坏的可能机制之一。研究表明，急性肺损伤患者血液和支气管肺泡灌洗液中NE的量和/或活性增加。相应地，经历急性肺损伤的动物血液和支气管肺泡灌洗液等中的NE活性增加。西维来司他钠（Sivelestat）是一种对NE具有高度特异性的NE合成抑制剂。许多研究表明，在几种急性肺损伤动物模型中，西维来司他治疗可改善肺部的炎症和水肿变化、提高生存率并降低NE活性。临床研究表明，西维来司他可改善与全身炎症反应综合征相关的这种损伤。与具有高分子量的内源性蛋白酶抑制剂相比，西维来司他这种合成的低分子量弹性蛋白酶抑制剂可能更容易、更有效地输送到炎症部位，并被认为可改善急性肺损伤的典型症状。西维来司他的临床应用将进一步阐明该化合物在临床急性肺损伤中的效用。
