Division of Cancer Medicine, Department of Gastroenterological Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan,
Dig Dis Sci. 2014 Apr;59(4):787-94. doi: 10.1007/s10620-013-2963-8. Epub 2013 Dec 8.
Sivelestat sodium hydrate (sivelestat) is a specific neutrophil elastase inhibitor that is effective in treating acute lung injury associated with systemic inflammatory response syndrome. As such, it may be useful in treating hepatic ischemia-reperfusion injury (IRI), a condition in which neutrophils transmigrate into the interstitium, leading to release of neutrophil elastase from neutrophils and consequent damage to the affected tissue, particularly in cases of hepatic failure after liver transplantation or massive liver resection.
The purpose of this study was to examine whether treatment with sivelestat inhibits neutrophil adhesion and migration to the vessel wall and suppresses hepatic IRI.
Whether and, if so, the extent to which sivelestat suppresses the adhesion and migration of neutrophils and reduces liver damage in hepatic IRI was examined in a human umbilical vein endothelial cell (HUVEC) model and a rat hepatic IRI model.
In the HUVEC model, the extent of the adhesion and migration of neutrophils stimulated by platelet-activating factor were found to be dose-dependently inhibited by sivelestat treatment (p < 0.05). In the rat model, serum liver enzyme levels were significantly lower at 12 h after reperfusion, and the number of neutrophils that had migrated to extravascular sites was significantly less in the treatment group compared to the control group (p < 0.05).
Sivelestat inhibits the adhesion and migration of neutrophils to vascular endothelium in hepatic IRI, thereby suppressing liver injury.
盐酸西维来司他钠（sivelestat）是一种特异性中性粒细胞弹性蛋白酶抑制剂，在治疗全身炎症反应综合征相关的急性肺损伤方面具有疗效。因此，它可能对治疗肝缺血再灌注损伤（IRI）有用，在这种情况下，中性粒细胞穿过血管壁间质，导致中性粒细胞弹性蛋白酶从中性粒细胞中释放，并对受影响的组织造成损害，特别是在肝移植或大量肝切除术后肝功能衰竭的情况下。
本研究旨在研究盐酸西维来司他钠治疗是否能抑制中性粒细胞黏附和迁移到血管壁，并抑制肝 IRI。
在人脐静脉内皮细胞（HUVEC）模型和大鼠肝 IRI 模型中，研究了盐酸西维来司他钠是否抑制中性粒细胞的黏附和迁移，并减轻肝 IRI 中的肝损伤，如果可以，其抑制程度如何。
在 HUVEC 模型中，发现盐酸西维来司他钠处理可剂量依赖性地抑制血小板激活因子刺激的中性粒细胞黏附和迁移（p < 0.05）。在大鼠模型中，再灌注后 12 小时血清肝酶水平显著降低，治疗组迁移到血管外部位的中性粒细胞数量明显少于对照组（p < 0.05）。
盐酸西维来司他钠抑制肝 IRI 中中性粒细胞黏附并迁移到血管内皮，从而抑制肝损伤。
